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Louis Pastettr 

5901 y^ 

OCT : 

Books by Rene J. Dubos 

The Bacterial Cell 

Bacterial and Mycotic Infections of Man 
Louis Pasteur 


By Rene and Jean Dubos 

The White Plague 


Louis Pasteur 




















Louis Pasteur 


by RENE J. D U B S 

With Illustrations 

Little, Brown and Company Boston 




Sixth Printing 

"Published simultaneously 
in Canada by McClelland and Stewart Limited 


To Jean 



i The Wonderful Century 3 

H The Legend of Pasteur 21 

m Pasteur in Action 58 

. iv From Crystals to Life 90 

v The Domestication of Microbial Life 116 

vi Spontaneous Generation and the Role of Germs in * 

the Economy of Nature 159 

vn The Biochemical Unity of Life 188 

* vm The Diseases of Silkworms 209 

- ix The Germ Theory of Disease 233 

x Mechanisms of Contagion and Disease 267 

xi Medicine, Public Health and the Germ Theory 292 

xn Immunity and Vaccination 317 

xin Mechanisms of Discoveries 359 

xrv Beyond Experimental Science 385 

Events of Pasteur s Life Arranged in Chronological 

Order 401 

Bibliography 405 

Index 409 


The author wishes to acknowledge his indebtedness 
HENREETXE NOUFFLABD for their help in securing photo- 
graphs of the portraits reproduced in this book. 

Monsieur Jean Joseph Pasteur; Madame Jean Joseph 
Pasteur. Pastel drawings of his father and mother 
made by Pasteur at the age of fifteen 26 

Pasteur at the age of thirty, professor at the University of 

Strasbourg 38 

Marie Laurent a few years before her marriage to Pasteur 38 

Pasteur, student at the Ecole Normale. Drawing made by 

Labayle from a daguerreotype 96 

Charles Chappuis, schoolmate and lifelong confidant of 

Pasteur. Drawing by Pasteur 96 

Jean Baptiste Dumas 102 

Jean Baptiste Biot 102 

Pasteur (approximately sixty-seven years old) 168 

Antoine J6r6me Balard 168 


Pasteur (approximately forty-five years old) at Pont Gisquet, 

dictating a scientific paper to his wife 228 

Pasteur and Pierre Bertin-Mourot 370 

Pasteur in his laboratory of the Ecole Normale. Reproduced 

from the Journal Illustre, March SO, 1884 370 

Louis Pasteur 



The W'ondei^Hi Century 

Although the roads to human power and to human 
knowledge lie close together, and are nearly the 
same, nevertheless ... it is safer to begin and raise 
the sciences from those foundations which have rela- 
tion to practice, and to let the active part itself be 
as the seal which prints and determines the con- 
templative counterpart. 


Louis PASTEUR was born on December 27, 1822, at Dole in the 
eastern part o France, where his father owned and managed 
a small tannery. When he died on September 28, 1895, at Ville- 
neuve FEtang near Paris, his name had already become legendary 
as that of the hero who had used science to master nature for 
the benefit of mankind. Many fields had been opened or enriched 
by his labors: the structure of the chemical molecule; the mecha- 
nism of fermentation; the role played by microorganisms in the 
economy of matter, in technology, in disease; the theory and 
practice of immunization; the policy of public hygiene. But the 
importance of his discoveries is not in itself sufficient to account 
for his immense fame. Among Pasteur's contemporaries, several 
equaled and a few surpassed him in scientific achievement, yet 
of him only was it said that "he was the most perfect man who 
has ever entered the kingdom of science/* For Pasteur's name 
evokes not only the memory of a great scientist, but also that of a 
crusader who devoted his life to the welfare of man. 

There were many traits in Pasteur's personality which enor- 
mously magnified the importance of his scientific contributions to 


society. His intense awareness of the problems of his environ- 
ment, his eagerness to participate in their solution, his passionate 
desire to convince his opponents, his indefatigable vigor and skill 
in controversy all these characteristics were as important as his 
experimental genius in making him not only the arm but also the 
voice, and finally the symbol, of triumphant science. 

In reality, Pasteur achieved this great popular success by the 
sacrifice of Egher ambitions7As a young man, he had planned to 
devote his life to the study of lofty theoretical problems: the 
fundamental structure of matter and the origin of life; but instead 
he soon began to devote more and more time to practical matters 
asking of nature questions relevant to the immediate preoccu- 
pations of his time. 

Although he was unquestionably one of the greatest experi- 
menters who ever lived, he did not create a new scientific phi- 
losophy as had Galileo, Newton, Lavoisier and the other men 
of genius that he so desired to emulate. Nevertheless, Pasteur kept 
to the end his youthful hope of gaming, through science, an 
insight into the problems of natural philosophy and in most 
of his writings, broad chemical and physiological theories are 
propounded side by side with details for the practical application 
of his discoveries. Nurtured in the classical tradition of the French 
Enlightenment, he worshiped the experimental method as the 
oracle which would reveal to man the universal laws of the 
physical world; as a child of the nineteenth century, on the other 
hand, he responded to the impact of the astonishing power dis- 
played by the exact sciences in solving the technical problems 
of industrial civilization. Indeed, he symbolizes the position 
reached by science in 1850, when experimental technology was 
replacing natural philosophy in the preoccupations of most scien- 
tific men. Theory and practice fought to rule Pasteur's life, as 
they did to control his times. 

Until the nineteenth century, society had demanded little from 
the man of science less than from the artist, who, according to 
the mood of the time, was expected to illustrate the Holy Scrip- 
tures, or to depict the sumptuous life of Pompeii or of Venice, 


or the bourgeois atmosphere of Flanders, or the pomp of 
Louis XIV. From the earliest times, true enough, mathematicians 
and physicists had served governments and princes as architects 
had built for them tombs and palaces, ramparts and catapults, 
harbors, ships, canals and roads while most naturalists, alche- 
mists and chemists had been physicians, devoting some of their 
talents to the art of healing or to compounding poisons. 

It had sufficed the man of science that his activities matched 
in general the preoccupations of his day; he might search for gold 
or for the elixir of life; he might investigate natural phenomena 
in order to make manifest the glory of God or satisfy the curiosity 
of man; or, at the most, he might devise a few instruments and 
techniques to make life easier and more entertaining. Yet science 
was predominantly the concern of the philosophical mind, more 
eager to penetrate the mysteries of the universe than to control 

This point of view had dictated the attitude even of those en- 
gaged in studies of immense practical importance. For example, 
Harvey, whose physiological discoveries were the beginning of 
scientific medicine, bequeathed his estate to the Royal Col- 
lege of Physicians with the stipulation that the proceeds be 
used "to search out and study the secrets of nature'*; he did not 
voice much interest in the practical consequences of this 

The men of genius of the seventeenth century had discovered 
many of the fundamental laws of the physical world. During the 
following century, the scientists of the Enlightenment exploited 
the philosophical consequences of these laws in the faith that 
they had arrived at a rational concept of the relation of man to 
the universe. Whether or not they erred in their premature con- 
clusions, this striving after aims which transcend the preoccupa- 
tions of everyday life justifies their claim to be recognized as 
"natural philosophers.*' That expression survived into the early 
nineteenth century, when Geoffroy Saint-Hilaire entitled his great 
work on the analogies of living creatures Philosophic anatomique. 
Even Faraday, on the eve of the profound industrial revolution 


which was to result from his electrical and chemical discoveries, 
preferred to be called a "philosopher," rather than a "scientist." 
It was perhaps as a silent protest against the encroachment of so- 
ciety into the activities of natural philosophers that, while still in 
full scientific productivity, he withdrew from all his consulting 
and industrial connections into the sanctuary of the Royal In- 

The integration of science and social economy, nevertheless, 
had had several isolated sponsors before Pasteur's time. Francis 
Bacon had pictured, in The New Atlantis, a society of scholars 
organized for the acquisition of a knowledge that would permit 
man to achieve mastery over nature. "The end of our Foundation/' 
he wrote, "is the knowledge of causes and secret motions of 
things; and the enlarging of the bounds of human empire, to the 
effecting of all things possible." In 1666 Colbert, that prototype of 
American efficiency who conducted the business of France under 
Louis XIV, had created the French Academy of Sciences and had 
supplied it with funds for the support of academicians, and of their 
instruments and experiments. As early as 1671, he organized a co- 
operative project for the survey of the kingdom and its depend- 
encies. Thus, under that Most Christian Monarch, King of 
France by Divine Right, was born a tradition which the leaders 
of Communist Russia were to follow systematically two hundred 
and fifty years later. In England, the Royal Society and the Royal 
Institution were founded for the cultivation of "such knowledge 
as had a tendency to use" and "to make science useful as well as 
attractive." When, in 1751, the French Encyclopedists, under the 
leadership of Diderot and d'Alembert, undertook the publication 
of a universal dictionary of arts, sciences, trades and manufac- 
tures, they devoted much of their attention to technical processes 
as carried out in workshops. "Should not," they asked, "the in- 
ventors of the spring, the chain, and the repeating parts of a 
watch be equally esteemed with those who have successfully 
studied to perfect algebra?" The Paris Academy of Sciences fol- 
lowed this lead and published, between 1761 and 1781, twenty 
volumes of illustrated accounts of arts and crafts. The activity of 


scientists everywhere then began to embrace practical applica- 
tions along with philosophical inquiries. 

An example was the study of power. The primitive steam 
engine was invented by Newcomen in 1705 and had been much 
improved by James Watt in 1765. As the use of the Watt engine 
spread, the need for evaluating the yield of energy per unit of 
fuel consumed, as a basis for improving the efficiency of the ma- 
chine, led the young French physicist Sadi Carnot to investigate 
the theoretical relation of heat to power. Study of this relation 
continued to occupy the minds of physicists. Joule, Meyer, Kel- 
vin and Helmholtz finally supplied the theoretical information 
from which the modem world learned to harness steam power for 
transportation and industry. Railroads, steamships, power plants 
of large factories soon emerged from the calculations and experi- 
ments of these scientists. 

The passage of electricity from the cabinet of the natural phi- 
losopher to workshops and homes was an even greater miracle 
to the man of the nineteenth century. In 1819, Oersted of Copen- 
hagen found that an electric current tended to twist a magnetic 
pole around it; and, shortly thereafter, the theory of the inter- 
action between currents and magnets was developed by Ampere, 
who also pointed out that the deflection of magnets by currents 
could be used for telegraphic transmission. It was not long before 
Morse and Wheatstone had made a practical reality of the electric 
telegraph. In 1823, Faraday showed that a wire carrying a cur- 
rent could be made to rotate around the pole of a magnet, and 
thus created the first electric motor. The electromagnet and the 
commutator were invented by Sturgeon during the next few years 
and, about 1830, the work of Joseph Henry in America and of 
Michael Faraday in England led to the discovery of electro- 
magnetic induction. The scientific armamentarium which made 
possible die dynamo and other electromagnetic machines was 
thus complete. 

Although the practical achievements of science during the 
early nineteenth century were most spectacular in the produc- 
tion and distribution of power, other scientific pursuits also helped 


to transform everyday life. For instance, when Daguerre and 
Niepce invented photography in 1835, "daguerreotypes" became 
overnight a popular fad, and frequently reached such a high level 
of technical perfection as to give them great documentary and 
artistic interest. Photography, it then appeared, was to do for the 
recording of the external forms of nature what printing had done 
for the recording of thought. 

Chemistry was abandoning the romantic den in which the 
alchemist had pursued the elixir of life and the dream of gold. 
Lavoisier, who initiated the modern era of theoretical chemistry, 
started his scientific life by collaborating in the preparation of an 
atlas of the mineralogical resources of France. Elected a member 
of the Royal Academy at the age of twenty-five, he prepared 
reports on a variety of technical problems. This made him familiar 
with the operations of most of the national industries: mines, iron 
and bleaching works, starch and soap factories, and others. He 
also improved the manufacture of saltpeter and gunpowder. It 
was in part his work on the Paris water supply and his interest 
in mineral waters that led him to investigate the chemistry of 
water, and his classical studies on the composition of air origi- 
nated from his efforts to design lanterns for the lighting of Paris. 

During the eighteenth and early nineteenth centuries France 
was leading Europe in theoretical and industrial chemistry, and 
her self-sufficiency during the Revolutionary and the Napoleonic 
Wars was in no small part the result of her scientific superiority. 

The place of chemistry in the economy of the rest of the world 
continued to expand after the Napoleonic Wars. Disasters like 
the mine explosion of 1812 near Gateshead-on-Tyne led Humphry 
Davy to study the behavior of firedamp, and to demonstrate that 
explosion would not pass through fine gauze. In 1816 he devised 
the safety lamp, which decreased the hazards in coal mining and 
thus contributed to the industrial supremacy of England. The 
synthesis of urea by Wdhler in 1828 opened the way for the 
synthesis of medicaments and dyestuffs. Even the technology of 
food was influenced by the new knowledge. Marggraf applied 


chemistry to the production of sugar from beetroot; the polari- 
scope permitted direct measurement of the concentration of sugar 
in crude extracts of the root; soon fields of sugar beets covered 
vast areas of northern Europe. 

Justus von Liebig organized in Giessen the first and most fa- 
mous laboratory of biochemistry. Stimulated by the desire to 
correct the poverty of the surrounding land, he undertook studies 
which elucidated the principles of soil fertility and led to the 
rational utilization of fertilizers. Scientific agriculture had begun. 
More than anyone else Liebig made the world conscious of the 
fact that even living processes would someday become amenable 
to chemical control. 

By the early part of the nineteenth century scientific knowledge 
was no longer the peculiar diversion of a few philosophers and 
curious minds. Whereas the technical advances of the eighteenth 
century in textiles, in the metallurgy of iron and steel, in power 
had been inventions, made by practical men, and were not 
based on the discoveries of experimental scientists, this relation- 
ship was obviously changing. More and more frequently, during 
the nineteenth century, research in the laboratory was preceding 
industrial applications. Scientific knowledge was becoming a 
source of wealth. 

Science had also become essential to the security of the state. 
True enough, the Committee of Public Safety had sent Lavoisier 
to the guillotine in 1794 with the statement that "The Republic is 
in no need of chemists/* but soon the statesmen responsible for the 
conduct of the French Revolutionary Wars had discovered their 
need for such scientists in time of emergency. "Everything," writes 
Maury in his history of the French Academy of Sciences, "was 
wanting for the defense of the country powder, cannons, pro- 
visions. The arsenals were empty, steel was no longer imported 
from abroad, saltpeter no longer came from India. It was precisely 
those men whose labours had been proscribed who could give to 
France what she wanted. On the basis of investigations begun 
by Lavoisier, Fourcroy taught the methods of extracting and 
refining saltpeter; Guyton de Morveau and Berthollet made 


known a new method of manufacturing gunpowder and studied 
the making of iron and steel; Monge explained the art of casting 
and boring cannons of brass for land use, and cast-iron cannons 
for the navy/* 

In the space of a few years, science had become a necessity to 
society. Bacon's dictum had come true: knowledge was power. 

Thus was born the tradition of mobilizing scientists to perfect 
the instrumentalities of war, and the importance of the military 
aspects of science has ever since grown in magnitude with each 
new conflict. During the Civil War in the United States, Joseph 
Henry became the chief adviser to the government on scientific 
military inventions, publishing several hundred reports, based on 
much experimentation. Out of this activity arose the National 
Academy of Sciences. Such was also the ancestry of the National 
Research Council and of the Office of Scientific Research and 
Development, organized in the United States during the First 
and Second World Wars respectively. Similar associations of 
scientists were created in the other belligerent countries, not only 
to devise weapons of offense and defense, but also to adapt the 
national economy to shortages of food and other supplies. 

The English blockade during the Napoleonic Wars greatly stim- 
ulated the development of practical chemistry in France. In order 
to foster the search for home products to replace colonial and for- 
eign goods, encouragement of all sorts was given to investigators; 
technical schools and colleges were established; exhibitions were 
promoted. Because France had been cut off from her usual sup- 
ply of crude soda, the Paris Academy of Sciences offered a prize 
which stimulated Leblanc's discovery of a method to make car- 
bonate of soda from salt. This in turn led, somewhat later, to the 
enormous development of the sulfuric acid industry in England 
and on the Continent. 

Just as the absence of cane sugar had encouraged the cultiva- 
tion of the sugar beet in the plains of northern France, it was to 
answer a state need that, stimulated by a prize offered by Na- 
poleon, Appert invented a method for the preservation of perish- 
able food. A few decades later, this method was improved by a 


Scottish firm Donkin, Hall & Gamble wMcli sold preserved 
food and meat to the English Navy, to the East India Company, 
and to the British and French governments during the Crimean 

As scientists came to occupy an increasingly important place 
in the affairs of the modern state, concern with scientific matters 
spread to broader areas of the population. 

Interest in science on the part of some laymen was not entirely 
new, of course: the fashionable salons had long accepted scien- 
tific discussions as a worthy subject for their intellectual if often 
artificial commerce. In most elegant terms, Fontenelle had writ- 
ten in 1686 his Entretiens sur la pluralite des mondes for refined 
and powdered marchionesses, but although his writings were 
accurate and skillful, literary predominated over scientific interest 
in his discussion of astronomy. Buffon and Voltaire had given 
to science a more philosophical tinge; and the Encyclopedists 
wrote informatively about it to educate the public. But with 
the Revolution came the descriptive, utilitarian and economic 
aspects of science soon displacing all others. It is interesting 
to recognize, in the proceedings of scientific academies of the 
time, some of the most notorious names of Revolutionary France. 
Marat lectured at Rouen and at Lyon on electricity and optics; 
Danton and Bonaparte competed for the Prix Raynal at Lyon, 
and Robespierre's name is connected with the Academy of Arras. 

Napoleon I professed a great interest in theoretical science. He 
discussed problems of celestial mechanics with Laplace, and took 
a large number of scientists with him during his Egyptian cam- 
paign. In 1807, he made a special court performance of the 
presentation of a report on the progress of sciences. Following the 
discovery of the electric current, he invited Volta to demonstrate 
his battery in Paris, where it aroused an enormous interest. He 
founded a medal with a prize of three thousand francs for the 
best experiment on "the galvanic fluid/' and despite the fact 
that France and England were then at war the medal was 


awarded to Humphry Davy in 1807. Again in the course of the 
war ? in 1813, he granted Davy permission to visit the volcanoes 
of Auvergne and the English party was honored and entertained 
by the French chemists and by the court, despite Davy's rudeness 
and arrogance. This trip, be it said in passing, was of considerable 
moment for the history of chemistry, since on that occasion Fara- 
day began his apprenticeship with Davy, and the latter received 
from conversations with Ampere information that led him to the 
discovery of iodine. 

The welcome granted by France to Humphry Davy in the 
midst of the war with England was a striking manifestation of that 
respect for culture and knowledge which transcended national 
rivalries during the early nineteenth century. It reflects also the 
glamour of the English chemist, who had achieved fame not only 
by his spectacular discoveries the electrolysis of water, the 
preparation of sodium and potassium, the chemistry of nitrous 
oxide and the anesthetic effect of this gas - but also by his genius 
as an exponent of science. In 1802 Davy had become professor 
of chemistry in the Royal Institution. It had been founded in 
1799 with the object of "diffusing knowledge and facilitating the 
general and speedy introduction of new and useful mechanical 
inventions and improvements; and also for teaching, by regular 
courses of philosophical lectures and experiments, the applica- 
tions of the new discoveries in science to the improvement of arts 
and manufactures." Although Davy devoted much care to the 
preparation of his lectures and demonstrations, he composed them 
only a few hours in advance, thus achieving in his presentation 
the immediacy of journalism. His rapidity of comprehension and 
performance appeared to the public as pure intuition and con- 
formed to the popular idea of genius. The success of his lectures 
increased from year to year, and soon established him in the 
fashionable life of London. His audience at the theater of the 
Royal Institution was close to one thousand, and included many 
of the celebrities of the time, among them Coleridge, who at- 
tended regularly in the hope of increasing his stock of literary 


When Davy was asked to lecture on chemistry and geology in 
Dublin in 1810, the rooms which had been arranged to hold five 
hundred and fifty persons proved much too small for the enthu- 
siastic audience. The charge for admission was two guineas but, 
when the supply of tickets had been exhausted, ten to twenty 
guineas were offered by those eager to attend. 

Faraday's lectures at the Royal Institution were no less success- 
ful than those of his celebrated predecessor. Despite his scorn of 
social life, Faraday was well aware of the significance of science 
for the public of his time and prepared in writing a careful analy- 
sis of the art of lecturing. When in 1861 he gave a course of 
lectures on "The Chemical History of the Candle," large audiences 
of school children gave up their Christmas holidays to hear 

John Tyndall followed Faraday at the Royal Institution and 
continued the great tradition of popular scientific lectures. In his 
published Fragments of Science he covered all fields of inquiry 
from the theory of color to the origin of tuberculosis. So great 
was his fame that the lectures on light which he delivered in the 
United States during the winter 1872-1873 gained him thirteen 
thousand dollars; even the rigorous winter weather of the Atlantic 
Coast could not discourage his large audiences in Boston, New 
York and Philadelphia. 

Throughout Western civilization, in the nineteenth century, 
the men of science established contact with a large and responsive 
public by means of lectures, books and pamphlets. Interest in 
von Humboldt's writings on cosmography proved an impetus to 
scientific explorations; Liebig published his famous Familiar Let- 
ters on Chemistry; Helmholtz brought to international audiences, 
beyond the German university towns where he lectured, his bril- 
liant views on the union of physics, physiology, psychology and 

Needless to say, biological problems also loomed large in the 
intellectual preoccupations of the day. During the early part of 
the century, the anatomist and paleontologist Cuvier became the 


eloquent voice of official French science. On February 15, 1830, 
Ms friend and scientific opponent Saint-Hilaire expounded before 
the Royal Academy of Sciences in Paris the doctrine of the unity 
of organic composition which, because it implied some form of 
transformism from a universal animal ancestor, was in conflict 
with Cuvier's belief in the fixity of species. Thus was launched a 
debate that lasted several months and that attracted wide notice. 
When either of the two champions was to speak, the visitors' seats 
were crowded and the grave academic hush was replaced by tense 
and eager excitement. 

Thirty years later, the publication of Darwin's Origin of Species 
was to open another debate which spread even more widely 
through the occidental conscience. In 1860, at Oxford, more than 
one thousand persons attended the historic meeting during which 
Huxley convinced his audience, at the expense of Bishop Wilber- 
f orce, that theories of science must be judged on the basis of fact 
and reason, not by the authority of dogma. The theory of evo- 
lution in this way became a part of social philosophy; the new 
scientific faith, Darwinism, tore Europe asunder as had the 
Reformation two centuries before. 

The first edition of 1250 copies of Origin of Species was sold 
out on the day of its publication (November 24, 1859). The 
second edition of SOOO copies was also snatched when it appeared 
six weeks later. Similarly, 8500 copies of Formation of Vegetable 
Mould through the Action of Worms, also by Darwin, were sold 
within three years. These numbers acquire greater significance 
when it is realized that neither of the two books had been written 
for the general public, and that a popular novel of the day would 
sell at the most 30,000 to 40,000 copies. In order to publish his 
First Principles Spencer issued a prospectus outlining the work 
and asking for subscribers, and arranged for publication in 
periodicals, as Dickens and Thackeray had published their writ- 
ings. With his article ProbUme de la physiologie g6n6rale, Claude 
Bernard brought the spirit of modern physiology to the lay readers 
of the Revue des Deux Mondes, and when, in 1865, he published 
his Introduction d T6tude de la m6decine exp&rimentale a large, 


educated public shared with the professional scientists an inti- 
mate understanding of the experimental method. 

Even the purely technical aspects of nineteenth-century science 
excited interest among laymen. Thus, in 1819, Chateaubriand 
found it worth while to mention the invention of the stethoscope 
by Laermec, and predicted a great future for the instrument in 
the study of cardiac and respiratory diseases. The first interna- 
tional loan exhibition of scientific apparatus was organized in 
London in 1876. In a single day, 11,969 persons visited the ex- 
hibits, to which many columns were devoted in The Times. Under 
the guidance of James Clerk Maxwell, Queen Victoria herself 
considered it proper to display great interest in the show, and 
listened with dignified attention to the description of the air pump 
and the Magdeburg hemispheres. 

Pasteur, as we shall see, was also to become involved in many 
public debates and in demonstrations of technical problems to 
laymen and artisans. When, in 1861, he delivered in the Sorbonne 
his famous lecture on spontaneous generation, one could recog- 
nize in the audience such celebrities as Victor Duruy, Alexandre 
Dumas senior, George Sand, Princess Mathilde. A few years later, 
a farm at Pouilly le Fort became a center of international interest 

when journalists and scientists, as well as farmers, assembled 
there to witness the demonstration that sheep could be immunized 
against anthrax. 

Medical science had become front-page news. 

As one reads the accounts of these great scientific performances 

the magnitude of the problems which were raised, the intel- 
lectual majesty of the scientists who were the main performers, 
the brilliance and responsiveness of the audience one returns 
with a sense of frustration to the dull scene where science and 
public come into contact in the present world. Yet the subject 
of the drama has remained no less exciting. Science is still the 
versatile, unpredictable hero of the play, creating endless new 
situations, opening romantic vistas and challenging accepted con- 


cepts. But the great actors no longer perform for the public, and 
tibe audience has lost its glamour. Gone are the days when such 
men as Davy, Faraday, Tyndall, Huxley, Helmholtz, Cuvier, 
Salnt-Hilaire, Arago, Bernard and Pasteur introduced in simple 
and elegant but also accurate terms the true concepts and 
achievements of science and the mental processes of scientists 
to appreciative audiences of children and adults, artisans and 
artists, earnest scholars and fashionable ladies. The great pageant 
of science is still unfolding; but now, hidden behind drawn cur- 
tains, it is without audience and understandable only to the play- 
ers. At the stage door, a few talkative and misinformed charlatans 
sell to the public crude imitations of the great rites. The world is 
promised cheap miracles, but no longer participates in the glo- 
rious mysteries. 

As a token of its respect for science, the nineteenth century 
bestowed upon many scientists honors and privileges as great as 
those which are today the monopoly of soldiers, politicians and 
businessmen. During Davy's illness in 1807, bulletins on the state 
of his health were issued similar to those published for royalty; 
eminent medical specialists refused to accept fees for their serv- 
ices. His convalescence stimulated public subscriptions which 
yielded sufficient funds for the construction of large voltaic bat- 
teries to be used in the furtherance of his work. Despite the early 
conflict between the doctrine of evolution and Christian dogma, 
Darwin, loaded with awards and honors during his lifetime, was 
buried with High Church ceremony in Westminster Abbey. In 
France, Cuvier remained one of the important personages of the 
state under Napoleon I, Louis XVIII and Charles X. The chemist 
Jean Baptiste Dumas and the physiologist Paul Bert passed from 
their chairs of the Sorbonne to the highest seats of government 
during the Second Empire and the Third Republic. Claude Ber- 
nard, Olympic in his aloofness from practical medicine, was made 
a senator without his asking; his funeral, like that of Darwin, was 
a national event attended by the highest officials of the state. 
Napoleon III entertained the famous men of science at court in 
Paris and Rambouillet. There Pasteur, even before the studies on 


the germ theory of disease had made his name an object of ven- 
eration, was invited to demonstrate with his microscope the teem- 
ing "world of the infinitely small" before the Emperor and his 
court in crinoline. 

During the days when an attack of hemiplegia threatened Pas- 
teur's life in 1868, the Emperor daily sent a personal courier to 
the house of the patient. Pasteur himself recounts with obvious 
pride that, at the International Congress of Physiology in Copen- 
hagen in 1884, the Queen of Denmark and the Queen of Greece, 
breaking all social etiquette, walked to him to greet him. In 1892 
France, now a republic, delegated her President to the Pasteur 
Jubilee, which took place at the Sorbonne and was attended by 
representatives from the whole world. In 1895, the national 
funeral of the great scientist was celebrated with a pomp that 
was to be equaled only by that of Victor Hugo, the hero of lit- 
erary France. 

The pageant of discoveries which thus revolutionized life dur- 
ing those exciting years, and the hope that man would soon com- 
plete his mastery over nature, created in the Western world an 
atmosphere of faith in science and an enthusiasm which was to 
find a somewhat naive expression in many books. 

In 1899, A. R. Wallace, who had proposed the theory of evo- 
lution simultaneously with Darwin, published under the title 
The Wonderful Century an enthusiastic account of the achieve- 
ments of his age. To the nineteenth century he credited twenty- 
four fundamental advances, as against only fifteen for all the 
rest of recorded history. Many of the great inventions and scien- 
tific theories listed by Wallace matured only during the second 
half of the century; but even while Pasteur was still a schoolboy, 
science was influencing habits, thought and language. 

In the sheltered atmosphere of the College of Besangon and of 
the Ecole Normale, Pasteur may not have felt the full impact of 
the social forces urging every scholar to devote his talent, knowl- 
edge and energy to the solution of practical problems. But when 
he became professor of chemistry and dean of the newly created 


Faculty of Sciences at Lille in 1854, the impact reached him 
through official channels. The decree organizing the new Science 
Faculties throughout France was very explicit; their role was to 
encourage the applications of science to the local industries. 
In a letter written during March 1855, the Minister of Public 
Education followed his appreciation of the success of Pasteur 
in his new functions by the following warning: "Let M. Pasteur 
be careful, however, not to be guided exclusively by his love for 
science. He should not lose sight of the fact that to produce use- 
ful results and extend its favorable influence, the teaching in 
the faculties, while remaining at the highest level of scientific 
theory, should nevertheless adapt itself, by as many applica- 
tions as possible, to the practical needs of the country." M. For- 
toul, Minister of Public Education in the conservative govern- 
ment of Napoleon III, would have been much surprised and 
disturbed had he recognized, in his recommendation to Pasteur, 
the echo of another statement made almost simultaneously by 
Karl Marx: "Hitherto, philosophers have sought to understand 
the world, henceforth they must seek to change it." 

In his letters from Paris and Strasbourg to his friend Chappuis, 
Pasteur talked of crystals as a lover of pure science, without ever 
referring to the possible role of his work in modifying the life of 
man. In response to his new responsibilities in Lille he soon be- 
came acutely conscious of wider social duties, emphasizing in 
his lectures the role of science in the practical life of the citizen 
and of the nation. Said he: "Where will you find a young man 
whose curiosity and interest will not immediately be awakened 
when you put into his hands a potato, when with that potato he 
produces sugar, with that sugar, alcohol, with that alcohol ether 
and vinegar? Where is he that will not be happy to tell his fam- 
ily in the evening that he has just been working out an electric 
telegraph . . . ? 

"Do you know when it first saw the light, this electric telegraph, 
one of the most marvelous applications of modern science? It was 
in that memorable year, 1822: Oersted, a Danish physicist, held 
in his hands a piece of copper wire, joined by its extremities to 


the two poles of a Volta pile. On Ms table was a magnetized 
needle on its pivot, and he suddenly saw, by chance you will say, 
but chance only favours the prepared mind, the needle move and 
take up a position quite different from the one assigned to it by 
terrestrial magnetism. A wire carrying an electric current deviates 
a magnetized needle from its position. That, gentlemen, was the 
birth of the modern telegraph . . /* 

He warned that there are not two forms of science pure and 
applied but only science, and the application of science. "With- 
out theory, practice is but routine born of habit Theory alone 
can bring forth and develop tibe spirit of invention." From then 
on, the applications of science were to loom large in his activi- 
ties; for he had tasted the intoxicating atmosphere which society 
provided for those who moved from the cabinet of the philoso- 
pher to the busy market place. His Me was henceforth to be 
divided between the serene peace of the laboratory and the full- 
blooded excitement which surrounds the application of science 
to practical problems. 

Pasteur was not alone in dedicating his genius to the service of 
a society intent on mastering the physical world. For example, 
William Thompson had also started by concerning himself with 
abstract scientific problems but soon felt impelled to facilitate 
the social desires of his times. First distinguished in theoretical 
physics and mathematics, he later was willing to devote more 
and more of his energy to the production of wealth. He it was 
who first organized a laboratory specially adapted to industrial 
research. A few decades later, Edison abandoned any pretense 
of interest in theoretical inquiries for their own worth, selecting 
his research problems only on the basis of the demands of the 
industrial markets around him. 

Thus, within a few generations, the scientist had evolved from 
natural philosopher to technologist. Were Michael Faraday and 
Claude Bernard, men who refused to become involved in the 
practical applications of their sciences, the greater for obeying 
the spiritual urge to pursue their theoretical inspiration to the 
very end, and for leaving to more limited minds the conversion 


of their findings into social commodities? It is too early to judge. 
The history o experimental science is far too short to permit an 
adequate perspective of its true relation to human welfare and 
to the understanding of the universe. 

But whatever the ultimate judgment of history, Wallace was 
right: the nineteenth was a wonderful century. Its scientists were 
masterful practitioners of the experimental method and, at the 
same time, they knew how to integrate their efforts into the heri- 
tage of classical ages. Faithful to the tradition of the Enlighten- 
ment, they never forgot, even while solving the technological 
problems of industrial civilization, that science is natural philoso- 
phy. In their hands, science was not only a servant of society, 
an instrument for the control of the physical world, but also an 
adornment of our Western culture. 


The Legend of Pasteur 

I learned this, at least by my experiment, that if one 
advances confidently in the direction of his dreams, 
and endeavours to live the life which he has imag- 
ined, he will meet with a success unexpected in com- 
mon hours. In proportion as he simplifies his life the 
laws of the Universe will appear less complex, and 
solitude will not be solitude, nor poverty poverty, 
nor weakness weakness. 


FEW LIVES have been more completely recorded than that of 
Louis Pasteur. His son-in-law Rene Vallery-Radot has presented, 
in La Vie de Pasteur, a chronological account of the master's 
origins, family life, labors, struggles, trials and triumphs. His 
grandson, Professor Pasteur Vallery-Radot, has reverently col- 
lected and published all his scientific and other writings, as well 
as his correspondence. The portraits painted by the young Louis 
in his home town at Arbois and at school in Besangon are readily 
available in private collections, and in the form of excellent re- 
productions. Emile Duclaux, one of Pasteur's students and early 
collaborators, his intimate associate to the end, has described and 
analyzed, in Pasteur: THistoire d'un Esprit, the evolution of the 
master's scientific mind and discoveries. The dwelling in which 
Pasteur was born, those in which he lived, toiled and died, are 
carefully maintained in their original condition as national 
shrines, helping us to recapture the atmosphere in which the son 
of a modest tanner moved from a quiet French province to 
become a legendary hero of the modern world. Numerous pho- 
tographs, statues, paintings and medals reveal the evolution 


from the young thoughtful schoolboy, through the stem profes- 
sor and eager experimenter of early adulthood, the passionate 
fighter and apostle of maturity, to the tired warrior dreaming 
in his old age. 

[ Secause Pasteur touched on so many problems and influenced 
so many lives during his tempestuous career, the different aspects 
of his personality are reflected as by a multif aceted mirror 
in the reaction to his performance of men at all levels of society 
and in all walks of life. There are many records of the admira- 
tion of his colleagues for his scientific discoveries, but also of 
impatience for his intolerence and overbearing attitude when he 
knew or believed that truth was on his side. Other philoso- 
phers and scientists shared his faith that the exact sciences con- 
stitutedoutside of revealed religion the only avenue to wis- 
dom and to power open to man; but there were also those who 
sneered at that naive philosophy, certain as they were that nature 
and truth would not be conquered by such primitive means. 
Countless human beings have worshiped him as the savior of 
their children or of their humble trades; but he had also to face 
the opposition of those who questioned the practical value of his 
discoveries sometimes on the basis of healthy and informed 
criticism, too often because man is blind and deaf to the new, 
or resents any changes to the old order of things. 

Soon, however, worship triumphed over criticism; legend cap- 
tured Pasteur from history. France took him as the symbol of 
her genius for logic and of her romantic impulses. His name now 
calls forth in French hearts poetical and haunting associations: 
the small towns of D61e and Arbois where he was born and 
raised, along graceful rivers called the Doubs and the Cuisance; 
Paris its great schools, the atmosphere of meditative scholar- 
ship and of feverish participation in the affairs of the world; a 
revered old man, exhausted by years of endless toil in the service 
of humanity, recalling under the huge trees of the park of Saint- 
Cloud the dreams of the idealistic student who fifty years 
earlier had planned to consecrate himself to the solution of 
some of the eternal problems of life. Across half a century, his 


voice still resounds with this message from a romantic age: "The 
Greeks have given us one of the most beautiful words of our 
language, the word "enthusiasm* a God within. The grandeur 
of the acts of men is measured by the inspiration from which they 
spring. Happy is he who bears a God within!" 
^ It is not in France alone that Pasteur has become a legendary 
hero. Scientific institutes, broad avenues, even provinces and vil- 
lages, carry his name all over the world. From monuments and 
statues, he supervises students entering halls of learning and 
watches over children playing in public squares. Even during his 
lifetime, "pasteurization" became a household word connoting 
healthy food and beverages. Had Pasteur lived in the thirteenth 
century, his silhouette would adorn the stained glass windows 
of our cathedrals; we would know him in the monastic garb of 
an abbot the founder of some new religious order or in the 
armor of a knight fighting a holy war. For, as much as a scientist, 
he was the priest of an idea, an apostle and a crusader. It is the 
champion of a cause, rather than the intellectual giant, that man- 
kind remembers under his name, and that an anonymous writer 
in the London Spectator of 1910 evoked in the following lines: 

There are more than sixty Pasteur Institutes: but I am 
tiiinking of the Paris Institute. At the end of one of its long 
corridors, down a few steps, is the little chapel where Pas- 
teur lies. . . . From the work of the place, done in the 
spirit of the Master, and to his honour, you go straight to 
him. Where he worked, there he rests. 

Walls, pavement, and low-vaulted roof, this little chapel, 
every inch of it, is beautiful: to see its equal you must visit 
Rome or Ravenna. On its walls of rare marbles are the 
names of his great discoveries Dyssymetrie Moleculaire. 
Fermentations . . . Generations dites Spontanees . . . 
Etudes sur le Vin . . . Maladies des Vers a Soie . . . 
Etudes sur la Biere . . . Maladies Virulentes . . . Virus 
Vaccins . . . Prophylaxie de la Rage. ... In the mosaics, 
of gold and of all colours, you read them again; in the 
wreathed pattern of hops, vines and mulberry leaves, and 
in the figures of cattle, sheep, dogs, and poultry. In the 
vault over his grave are four great white angels, Faith, 


Hope, Charity, and Science. From time to time Mass is said 
in the chapel: the altar is of white marble. Twice a year, 
on the day of the master's birth and the day of his death, 
the workers at the Institute, the "Pasteurians," come to the 
chapel, some of them bringing flowers in memory of him, 
and afterwards pay a visit of ceremony to Madame Pas- 
teur, whose apartments are on the second floor of the In- 
stitute, above the chapel. . . . 

Yet, to me, who remember him, saw him, heard him talk, 
shook hands with him, all the adornments round his grave 
were not sufficient, and the half was not told me. For he 
was, it seems to me, the most perfect man who has ever 
entered the kingdom of Science. . . . Here was a life, 
within the limits of humanity, well-nigh perfect. He worked 
incessantly: he went through poverty, bereavement, ill- 
health, opposition: he lived to see his doctrines current over 
all the world, his facts enthroned, his methods applied to a 
thousand affairs of manufacture and agriculture, his science 
put in practice by all doctors and surgeons, his name praised 
and blessed by mankind: and the very animals, if they could 
speak, would say the same. Genius: that is the only word. 
When genius does come to earth, which is not so often as 
some clever people think, it chooses now and again strange 
tabernacles: but here was a man whose spiritual life was no 
less admirable than his scientific life. In brief, nothing is too 
good to say of him: and the decorations of his grave, once 
you know his work, are poor, when you think what he was 
and what he did. Still, it is well that he should lie close to 
the work of the Institute, close to the heart of Paris, with 
Faith, Hope, Love and Science watching over him. 1 

Thus the son of a former sergeant in Napoleon's army had 
found his place in the golden legend of the modern world. 

After the collapse of the Emperor, Sergeant Jean Joseph Pas- 
teur had taken refuge in the humble profession of tanning first 
at Dole, then at Arbois in eastern France. A crude painting which 
he made, of a man in a soldier's uniform, leaning on the plow 
while gazing into a distant dreamland, suggests that the peaceful 

1 We have been informed by the editor of the Spectator that this article 
was written by Stephen Paget (1855-1926) F.R.C.S., Vice Chairman 
Research Defence Society, and author of several medical and historical books. 


citizen had not forgotten the intoxicating dreams of the imperial 
epic; and yet, perhaps because he was tired from having seen 
too many social and military upheavals, all he desired for his 
son was that he should rise above the status of the small business- 
man into the safe if obscure dignity of a teaching appointment 
in the provincial secondary school In the melancholy eyes of 
the portrait of his father painted by the young Louis Pasteur in 
1837, one recognizes the resigned wisdom of so many sensitive 
and reflective citizens of the old European communities, to whom 
history has given the vicarious excitement of adventure and of 
political progress, but who also know that society exacts a painful 
toll of those who want to rise above its norm. In his many letters 
to his son away at school first in Besanon, then in Paris the 
old soldier expressed a homely philosophy, seeing in excessive 
social or intellectual ambition a danger far greater than those 
lurking in wicked Paris. "There is more wisdom in these hundred 
liters of wine," he would assure his overeager son, "than in all 
the books of philosophy in the world." 

But despite this counsel of resignation, Jean Joseph Pasteur 
devoted his own evenings, after the hard days of labor in the 
tannery, to reading in history books some accounts of the past 
glories of France, and to acquiring the education which ap- 
peared to him the symbol of greater human dignity. How much 
yearning for a broader life appears in the efforts of the old 
soldier, attempting to understand in later life the scientific 
achievements of his son, and to educate himself in order to be- 
come the advocate of learning for his turbulent daughters! 

Louis Pasteur's mother forms the silent and poetical back- 
ground of this delightful family picture. We see her draped in 
a lovely shawl, with all the dignity of a provincial housewife, 
in a masterly pastel made by Louis at the age of fifteen. And 
behind the charm of her disciplined face, one can read all the 
emotional intensity which inspired her to write to her son on 
January 1, 1848, shortly before her death: "Whatever happens, 
do not become unhappy, life is only an illusion." 

Nothing obvious in the home atmosphere of the young Louis 


Pasteur appeared designed to prepare him for the exciting role 
which he was to play in science and society. His peaceful and 
humble family, the gentle, comfortable and settled country in 
which he was bom and raised, his teachers' disciplined accept- 
ance of a limited environment all invited him to a quiet life, 
adorned but not monopolized by study. Outwardly, he appears 
as a sentimental, hard-working boy, serious-minded, dutiful, eager 
to assimilate from the well integrated atmosphere of his environ- 
ment the classical culture of France, the knowledge of the glo- 
rious role that his country had played in the history of Western 
civilization. When he left his native province for the great cen- 
ters of learning in Paris, it was not to find the answer to some 
soul-searching query, not for the sake of intellectual adventure, 
not with the ambition of the social conqueror. It was merely as 
an earnest student, going where teaching was most enlightened in 
order to prepare himself as best he could for a worth-while place 
in his community. He had not yet dreamed that fate had selected 
him for a historical role to be played beyond his native province 
and even beyond France a legend in the annals of humanity. 

At least, there is nothing to reveal that the magic wand had 
yet tapped him when he entered the great Ecole Normale 
Superieure in Paris. Only the fact that he had engaged in por- 
trait painting between the ages of thirteen and eighteen dif- 
ferentiated him slightly from the ordinary good student. However 
skillful, these portraitures were no more than the conscientious 
expression of his immediate surroundings his father, his mother, 
the town officials and notables, a picturesque old nun and his 
school friends all witnesses of the vigorous but settled life of 
his town and school. 2 But who knows what strivings and urges 

2 The Finnish artist Albert Edelfeldt, who painted a famous portrait of 
Pasteur in his laboratory in 1887, expressed in a letter to one of his friends 
the following judgment on Pasteur as a painter: "Outside of science, painting 
is one of the few things that interest him. At the age of 16, he had intended 
to become a painter and amused himself making pastel drawings of his 
parents and of other citizens of Arbois; some of these pastels are in his home 
at the Institute and I have looked at them very often. They are extremely 
good and drawn with energy, full of character, a little dry in color, but far 











such humble efforts conceal? The travels of the explorer into 
the dangerous and unknown, the literary and artistic projections 
of imaginative wanderings into unusual or unreal worlds, the 
visions of wild dreams, certainly are not the only manifestations 
of the restless mind. The mere copying of one's environment may 
at times be a naive effort to dominate the world by an act of 
re-creation. And so Pasteur may have begun, in these youthful 
portraits, an attempt at the intellectual mastery and control of 
his environment. 

Like his schooling, his early letters and writings fail to give an 
obvious omen of the adventurous lif e he was to live. To his par- 
ents, he faithfully recorded conscientious scholastic efforts; to his 
mother, he recommended that she not interfere with his sisters* 
schoolwork by too many small household chores; to his sisters, 
he advised good behavior and diligent study. 

"Work, love one another. Work . . . may at first cause disgust 
and boredom; but one who has become used to work can no 
longer live -without it ... with knowledge one is happy, with 
knowledge one rises above others." 

**. . . Action, and work, always follow will, and work is almost 
always accompanied by success. These three things, will, work 
and success, divide between themselves all human existence; 
will opens the door to brilliant and happy careers; work allows 
one to walk through these doors, and once arrived at the end 
of the journey, success comes to crown one's efforts." 

This rigid sense of discipline was softened by a great senti- 
mentality and a profound devotion to his family, friends and 
country. He read edifying books and attempted to mold his life, 
and that of others, according to their teachings. So strong was 

superior to the usual work of young people who destine themselves to an 
artistic career. There is something of the great analyst in these portraits: 
they express absolute truth and uncommon will power. I am certain that 
had M. Pasteur selected art instead of science, France would count today 
one more able painter. . . ." 


"his attachment to the tome atmosphere that when he first went 
to school in Paris he could not conceal in his letters many a 
pathetic expression of loneliness. "Oh! what would I not give 
for a whiff of the old tannery!" and he returned to Arbois for 
a year before again gathering enough courage to go and meet 
his destiny in the capital. 

His father, mother and sisters, and later his wife and children, 
constituted his emotional universe, supplemented by a very few 
friends, and by some of his masters upon whom he bestowed un- 
bounded devotion. Chappuis and Bertin, comrades of his youth, 
remained his confidants to the end. And to the old family home 
in Arbois he returned every summer, and in periods of familial 
tragedies, there to recover physical and moral strength. From his 
father, and from his schoolbooks, he learned to identify his life 
with that of France, and he maintained unaltered until his death 
a deep loyalty to family, friends and country. 

Not until he was twenty-five do his writings express a philo- 
sophical query, an overwhelming question; they state, rather, 
with a force born of good upbringing, only the moral standards 
of his environment and his determination to live according to 
them. Is it not possible, however, that even this homely philoso- 
phy may at times be the product of an intense pressure to escape 
from oneself and one's environment? Most adolescents experience 
the urge often obsessing to grow above and beyond their 
physical needs and comforts, long before an ideal or an objective 
has been recognized toward which to proceed. Perhaps, in the 
life of many, the direction in which one goes, the special nature 
of the outlet, is of far less importance than the opportunity to 
move, to transcend oneself, to emerge from plant and animal 
life into these immensely varied areas which are the reserved 
hunting grounds of the human mind. 

Pasteur did not early find the formula of his life, except that it 
should be devoted to work and to some worth-while cause. His 
immediate environment did not suggest any field in which he 
could expand, any channel in which he could direct his energy. 
There was seemingly no overpowering interest, no philosophical 


question or scheme to harness his mind, no passionate urge to 
monopolize his thoughts. In haphazard manner he responded, 
at first, to any voice which pleaded before him with a respectable 
argument^ As a student, in Besangon or in Paris, his dominating 
preoccupation was to reach the top of Bis class in mathematics, 
physics and chemistry; and he often succeeded, through appli- 
cation and industry. Admitted in 1842 to the scientific section 
of the Ecole Normale Superieure, he refused to enter the school 
because he had been received as only the sixteenth in his class; 
he competed again the following year, to be readmitted as fifth in 
rank. Training himself to become a professor, he begged the 
famous chemist, Jean Baptiste Dumas, to accept him as a teaching 
assistant not, he assured him, that he wanted the job for the 
sake of money or for the purpose of forming a closer acquaintance 
with an important man, but because he had "the ambition to 
become a distinguished professor" "My chief desire is ... to 
secure the opportunity to perfect myself in the art of teaching." 
To his friend Chappuis, he wrote with pride that he had been 
highly successful in his practical classroom test as a teacher of 
physics and chemistry. "M. Masson told me that . . . my lesson 
in physics was good, the one in chemistry was perfect. . . . Those 
of us who are to become professors must make the art of teaching 
our chief concern." And, in fact, it is at this level that his in- 
structors judged him. "Will make an excellent professor," was the 
laconic and uninspired comment which ushered him into the 
world from the Ecole Normale. 

Within the walls of the old school, however, Pasteur had 
already received, unknown to his schoolmates and to most of his 
instructors, tie visitation of the Muse of Science. The dutiful 
student was no longer satisfied with being a passive recipient of 
knowledge, or even with the prospect of merely passing it on to 
others. He had tasted the excitement of discovery. The passion 
the almost insane urge to move on into the unchartered lands 
of nature had taken hold of him. 

The investigator was beginning to claim precedence over the 


professor. It was while repeating some classical experiments on 
the formation and properties of crystals that he became aware of 
the world of mystery hidden behind the polished teaching of text- 
books and professors. From then on, the torment of the unknown 
became a dominating component of his life. But even before this 
revelation, he had received from Dumas the spark which had 
fired his eagerness to understand the chemical laws governing 
the world of matter, and his awareness of the power that chem- 
istry could exert in the affairs of man. 

Like many chemists and physiologists of the nineteenth cen- 
tury Liebig and Claude Bernard for example Dumas had be- 
gun his scientific career as apprentice to an apothecary, at a time 
when pharmacy had not yet degenerated into the distribution of 
ready-made, highly advertised packages. From Alais in the South 
of France, where he was born in 1800, Dumas had gone to study 
in Geneva. It was as a young pharmacist that he had signed the 
studies on iodine, blood, muscle contraction and plant physiol- 
ogy which first made his name familiar to European scientists. In 
Paris, he soon became one of the scientific leaders and one of the 
founders of organic chemistry. He formulated in particular the 
theory of substitution of chemical radicals, then the theory of 
alcohols and of fatty acids, and finally devoted himself, with his 
friend Boussingault, to the study of the chemical changes asso- 
ciated with living processes. These strenuous studies did not suf- 
fice to satiate his creative vigor, for he retained the exuberance, 
generosity and communicativeness of the sunny land of his birth. 
He was not only a leader in science but even more a leader of 
men, and soon found himself engaged in the reorganization of 
higher education. An influential senator and minister during the 
Second Empire and the Third Republic, he sat in all committees 
concerned with the relation between science and society. He 
loved authority, not for the mere sake of exercising power, but 
because he had a physiological need to operate on a large scale, 
to spend his varied and great talents on matters of national inter- 
est. He liked to recognize and support ability and genius. He was 
one of the first who guessed how much Pasteur would contribute 


to science and to France, and he never spared his influence and 
his wisdom to encourage and guide the younger man who was his 
student, then his colleague, and always his friend and admirer. 
With similar vision and generosity, Dumas had protected 
Daguerre during the fifteen years when the inventor of photog- 
raphy had to struggle against technical difficulties, and against 
the ridicule surprising to us as it is that his contemporaries 
first poured upon him. 

Dumas was a great teacher. He brought to the lecture room 
the authority of his name, an immense sense of the dignity of his 
calling, and an eloquence made of the thorough preparation of 
his delivery and of the warmth of his meridional accent. On the 
days when he taught his course at the Sorbonne, the eight hun- 
dred seats of the amphitheater were filled with a varied audience 
attracted by the great manner of the chemist, as much as by the 
subject which he taught. Fortunately, the first row was reserved 
for the students of the Ecole Normale, and the enthusiastic Pas- 
teur came out of each lecture intoxicated with vast projects. 
Pasteur retained for Dumas a veneration which he never tired of 
expressing, and he often spoke of the unforgettable days when 
his rnind and his heart had been opened by the great teachers 
whom he called allumeurs (fame. Those had been his greatest 
emotions, and at the end of his own glorious life, he liked to refer 
to himself as the disciple of the enthusiasms that Dumas had 

While still a student, Pasteur had attracted the attention of 
another celebrated chemist, Antoine J6r6me Balard, who was 
then professor at the Ecole Normale. Like Dumas, Balard was a 
Southerner and had been a druggist's apprentice. He had dis- 
covered bromine at the age of twenty-four and had increased his 
fame in Parisian scientific circles by a delightful contempt for 
the conventions of social life. Even after becoming a member 
of the Institut de France, he continued to live in a primitive 
student room furnished with two old shaky armchairs painted 
with his own hands in a peculiar red color, under the illusion 
that he was imitating mahogany. When traveling, his total lug- 


gage consisted of a shirt and a pair of socks* wrapped in a news- 
paper, which he would slip into his large pocket. He had adopted 
in his work the same simplicity which ruled his daily life. Hav- 
ing read in the writings of Benjamin Franklin that a good work- 
man should know how to saw with a file and to file with a saw, 
he liked his students to work without equipment. He rejoiced at 
seeing Pasteur compelled to build with his own hands the 
goniometer and polarimeter needed for crystallographic studies, 
as well as the incubator in which were carried out the classical 
experiments on fermentation and spontaneous generation. As is 
often indeed, usually the case, Balard made most of his dis- 
coveries while working without means, on a comer of his apothe- 
cary's bench. When he became professor of chemistry at the 
Ecole Normale, now occupying new quarters in the Rue d'Ulm, 
he cheated the administration out of a few rooms by pretending 
that they were to be used for the display of collections; he trans- 
formed them into research laboratories. There also he put a bed, 
so as to become even more independent of conventional life. It 
was in these humble quarters that Balard took on young Pasteur 
as his assistant. By that time, however, he had become so much 
more interested in the work of others than in his own that he let 
the young student go his own way and merely encouraged him 
with his jovial optimism. 

Balard, fanciful in his habits and picturesque in the vehemence 
of his speech and gestures, was also a man of strong convictions. 
When he heard that Pasteur was to be sent to a small secondary 
school far away from Paris by administrative order from the 
Ministry of Education, he unleashed a one-man campaign against 
the decision, and the Ministry had to yield under the barrage of 
a torrent of words. Pasteur was allowed to spend an additional 
year at the Ecole Normale, and remained always grateful to his 
master for this timely help. With ever-increasing industry, he 
now devoted all his spare time to chemical experiments in Balard's 

Delafosse, one of the chemistry instructors, had published a 
conscientious study dealing with the geometrical, physical and 


chemical properties of crystals. The elegance and precision of 
this field of research appealed to the neat and orderly Pasteur. 
Moreover, it soon provided him with a specific question worthy 
of his industry and imagination. He had read in the school library 
a recent note in which the celebrated German crystallographer 
and chemist Mitscherlich had stated that the salts of tartaric and 
paratartaric acids, although identical in chemical composition and 
properties, differed in their ability to rotate the plane of polarized 
light. This anomaly had remained in Pasteur's mind as an obsess- 
ing question, and it was to clarify it that he undertook the study 
which led him to recognize that paratartaric acid was, in reality, 
a mixture of two different tartaric acids possessing equal optical 
activity, except for the fact that one (the right or dextro form) 
rotated a polarized beam of light to the right, whereas the other 
(the left or levo form) rotated light to the left. The genesis and 
significance of this discovery will be discussed in succeeding 
chapters. Suffice it to point out here that Pasteur had demon- 
strated, with one stroke, independence of mind in questioning 
the statement of a world-famous scientist, imagination in recog- 
nizing the existence of an important problem, and experimental, 
genius in dealing with it. He had exhibited extraordinary power 
of detailed observation, a superb competence in planning the 
strategy and tactics of his experimental attack, tireless energy 
and meticulous care in its execution. 

Pasteur had become interested in crystal structure before realiz- 
ing that this study would lead him into questions of immense 
theoretical significance, but the implications of his findings soon 
became apparent to him. That he found the problem worthy of 
his metal is obvious from the enthusiasm displayed in a letter 
to his friend Chappuis: "How many times I have regretted that 
we did not both undertake the same studies, that of physical 
sciences! We who so often used to speak of the future, how little 
we understood! What beautiful problems we would have under- 
taken, we would undertake today, and what could we have not 
solved, united in the same ideas, the same love of science, the 
same ambition? I wish that we were again twenty and that the 


three years of the School were to start under these conditions/* 
Again a few years later he wrote to his friend: "That you were 
professor of physics or chemistry! We would work together and 
within ten years, we would revolutionize chemistry. There are 
marvels hidden behind the phenomenon of crystallization, and its 
study will reveal some day the intimate structure of matter. If 
you come to Strasbourg, you will have to become a chemist de- 
spite yourself. I shall speak to you of nothing but crystals." 

Balard took great personal pride in the work done in his labora- 
tory by the young Pasteur and, with his customary exuberance 
and loud voice, soon undertook to promote it during conversations 
at the meetings of the Paris Academy of Sciences. Among Ms lis- 
teners none was more interested even though somewhat skep- 
tical than the veteran physicist, Jean Baptiste Biot. 

Biot was then seventy-four. Aloof from the world, he main- 
tained a haughty independence, based on immense scientific and 
literary culture and on the most exacting ideals. He denounced 
sham and pretense wherever he found them, irrespective of the 
consequences of his actions, undisturbed by the enmity that he 
caused; when later he became convinced that the influential 
Balard no longer took an active part in research, he fought alone 
against his appointment to the chair of chemistry at the Sor- 
bonne. Speaking of his scientific colleagues who affected to dis- 
dain letters and who were careless in their use of the noble French 
language, he publicly said with scorn: "I do not see that the 
quality of their science becomes the more obvious for their lack 
of literary culture." Among his many scientific achievements, Biot 
counted some of the pioneer work on the ability of organic com- 
pounds to change the direction of polarized light (optical activ- 
ity), and he immediately perceived, therefore, the importance of 
the separation of paratartaric acid into two opposite forms of 
tartaric acid. Unconvinced by Balard's heated reports, however, 
he demanded to see the evidence which justified these extraor- 
dinary claims. 

To a letter from Pasteur asking for an interview, Biot replied 
with his usual dignity: "I shall be pleased to verify your results 


if you will communicate them confidentially to me. Please believe 
in the feelings of interest inspired in me by all young men who 
work with accuracy and perseverance/* 

An appointment was made at the College de France where 
Biot lived, and there the young Pasteur demonstrated the validity 
of his claims to the distinguished master. From that day on 
began, between Pasteur and Biot, one of the most exquisite rela- 
tionships in the annals of science, made up of filial affection, of 
common ideals and interests, of respect and admiration. 

The warm and sensitive heart which Biot hid beneath his aus- 
terity and skepticism becomes manifest in a note from him to 
Pasteur's father: "Sir, my wife and I appreciate very much the 
kind expressions in the letter you have done me the honour of 
writing me. Our welcome to you was indeed as hearty as it was 
sincere, for I assure you that we could not see without the deepest 
interest such a good and honorable father sitting at our modest 
table with so good and distinguished a son. I have never had 
occasion to show that excellent young man any feelings but those 
of esteem founded on his merit, and an affection inspired by his 
personality. It is the greatest pleasure that I can experience in 
my old age, to see young men of talent working industriously and 
trying to progress in a scientific career by means of steady and 
persevering labour, and not by wretched intriguing," To Pasteur 
himself Be wrote, following this visit: "We highly appreciated 
your father, the rectitude of his judgment, his firm, calm, simple 
reason, and the enlightened love he bears you." And shortly 
before his death he gave his photograph to Pasteur, with these 
words as a further symbol of his affection: "If you place this 
portrait near that of your father, you will unite the pictures of 
two men who have loved you very much in the same way." 

Despite the vigorous protests of Dumas, Balard and Biot, and 
of other eminent members of the Academy, Pasteur could no 
longer escape the decision of the Ministry of Education to send 
him off as was the custom to a teaching appointment away 
from Paris. In 1847, he took up his new post in Dijon where he 


taught elementary physics with his usual thoroughness, while 
lamenting the lack of time and facilities for his investigations. 
Soon, however, his sponsors obtained for him a better appoint- 
ment at the University of Strasbourg, where in January 1848 
he became acting professor of chemistry. In Strasbourg began 
one of the richest and happiest periods of his life. 

He took quarters in the house of Pierre A. Bertin-Mourot, 
professor of physics on the faculty, whom he had known while 
at school in Besangon and at the Ecole Normale. A conscientious 
and able teacher, equally devoted to his students and to his 
friends, Berlin brought into Pasteur's life the smiling help of 
a benevolent philosophy appreciative of wine, beer and all the 
simple pleasures of a normal existence. To Pasteur's intensity, 
impetuosity and lack of humor, he opposed an amiable skep- 
ticism, a robust heartiness, balanced by great common sense and 
an exacting conception of duty. This excellent man wanted his 
efforts to remain unknown be they concerned with the pains 
he took in preparing his lectures or with the help that he so 
generously gave to others because, as he put it, "they are my 
own business/' He remained Pasteur's close friend throughout 
life, and when later he became assistant director of the Ecole 
Normale in replacement of Pasteur, his jovial and generous atti- 
tude once more helped to ease the tension of the stormy life of 
his famous colleague. 

A letter from his father reveals that Pasteur made plans to 
arrange his life in a more permanent manner as soon as he arrived 
in Strasbourg: "You say that you will not marry for a long time, 
that you will ask one of your sisters to live with you. I would 
like it for you and for them, for neither of them wishes for a 
greater happiness. Both desire nothing better than to look after 
your comfort; you are absolutely everything to them/* 

These plans were soon to be modified for, in the meantime, 
Pasteur had been introduced to the home of the University Rec- 
tor, M. Laurent. He wrote him the following letter on Febru- 
ary 10, 1849 to ask for his daughter, Marie Laurent, in mar- 



An offer of the greatest importance to me and to your fam- 
ily is about to be made to you on my behalf; and I feel it 
my duty to put you in possession of the following facts, 
which may have some weight in determining your accept- 
ance or refusal. 

My father is a tanner in the small town of Arbois in the 
Jura. I have three sisters. The youngest suffered at the age 
of three from a cerebral fever which completely interrupted 
the development of her intelligence. She is mentally a child, 
although adult in body. We expect to place her shortly in a 
convent where she probably will spend the rest of her lif e. 
My two other sisters keep house for my father, and assist 
him with his books, taking the place of my mother whom 
we had the misfortune to lose May, last. 

My family is in easy circumstances., but with no fortune; 
I do not value what we possess at more than fifty thousand 
francs, and I have long ago decided to hand over my share 
to my sisters. 1 have therefore absolutely no fortune. My 
only means are good health, some courage, and my position 
in the University. 

I left the Ecole Normale two years ago, an agrege in 
physical science. I have held a doctor's degree eighteen 
months, and I have presented to the Academy of Sciences 
a tew works which have been very well received, especially 
the last one, and upon which tbere is a report which I have 
the honor to enclose. 

This, Sir, is all my present position. As to the future., un- 
less my tastes should completely change, I shall devote my- 
self entirely to chemical research. I hope to return to Paris 
when I have acquired some reputation through my scien- 
tific studies. M. Biot has often told me to think seriously 
about the Academy; I may do so in ten or fifteen years* 
time, and after assiduous work; but this is only a dream, and 
not the motive which makes me love science for science's 

My father will himself come to Strasbourg to make the 
proposal of marriage. No one here knows of the project 
which I have formed and I feel certain, Sir, that if you refuse 
my request, your refusal will not be known to anyone. . . . 

P.S. I was twenty-six on December 27. 


Thus, Pasteur took this most important step of his personal life 
a few weeks after having first met Marie Laurent, with the same 
impetuosity that led him to rapid and at times instantaneous de- 
cisions in his scientific career. His published letters to Marie 
Laurent give some measure of the intensity of his emotion: "I 
have not cried so much since the death of my dear mother. I woke 
up suddenly with the thought that you did not love me and im- 
mediately started to cry. . . " "My work no longer means any- 
thing to me. I, who so much loved my crystals, I who always used 
to wish in the evening that the night be shorter to come back the 
sooner to my studies." But the disturbance caused in his life of 
labor by this sentimental explosion was only a ripple which did 
not really disturb the stream of discoveries and Pasteur resumed 
his scientific work immediately after his marriage on May 29. 
Many tragedies deeply affected his private life in subsequent 
years; the loss of his beloved father, the early deaths of two of 
his daughters and of his sister, the paralysis which struck him 
in 1868. But the ideal atmosphere of his conjugal life helped him 
to withstand these trials and to pursue uninterrupted the course 
of his productive life. 

Marie Laurent was twenty-two at the time of her marriage 
a gentle, graceful blue-eyed girl with a pleasant singing voice, 
whose joy of living mounted in silver tones as she went through 
her household duties. This gaiety of spirit she retained through- 
out the strenuous years ahead. When he proposed to her, Pasteur 
had nothing to offer but a life of study within modest material 
circumstances. At the most he could, iqi a moment of confidence, 
promise to gain immortality for their name. Madame Pasteur 
played her part in assuring this immortality by consecrating her- 
self to her husband and to his dreams, and molding her behavior 
to fit the goal which he had formulated for their life. She ac- 
cepted many limitations: a professor's small salary; his turning 
over to the purchase of scientific equipment the additional income 
derived from prizes; his odd mannerisms carried from the labora- 
tory into the atmosphere of the home; and always the knowledge 
that work came first, even before the normal pleasures of a simple 


home life. She could write to her children in 1884: "Your father 
is absorbed in his thoughts, talks little, sleeps little, rises at dawn, 
and in one word continues the life I began with him this day 
thirty-five years ago." 

All this, she understood and tolerated. The great part which 
she played in the achievements of the master has been described 
by Roux, who was Pasteur's associate for twenty years: 

"From the first days of their common life, Madame Pasteur 
understood what kind of man she had married; she did every- 
thing to protect him from the difficulties of life, taking onto her- 
self the worries of the home, that he might retain the full free- 
dom of his mind for his investigations. Madame Pasteur loved her 
husband to the extent of understanding his studies. During the 
evenings, she wrote under his dictation, calling for explanations, 
for she took a genuine interest in crystalline structure or attenu- 
ated viruses. She had become aware that ideas become the clearer 
for being explained to others, and that nothing is more con- 
ducive to devising new experiments than describing the ones 
which have just been completed. Madame Pasteur was more 
than an incomparable companion for her husband, she was his 
best collaborator.** 

When she died in 1910 she was laid to rest near the com- 
panion with whom she had so completely identified her life. Be- 
cause she was in truth the faithful partner of his human and 
divine mission, it is fitting that the Roman words Socia rei 
humanae atque divinae should have been engraved on her tomb. 

The Strasbourg years reveal, in a forceful and often picturesque 
manner, the qualities which were to make of Pasteur one of the 
most adventurous and at the same time one of the most effective 
experimenters of his time. It is difficult, indeed, to visualize how 
the young and inexperienced professor could produce, against 
what would be for others the handicap of domestic happiness, 
such a varied harvest of new facts, scientific theories, and philo- 
sophical dreams. He had come to realize that the optical activ- 
ity of organic substances could be used as a tool for the study 


of molecular structure; deep in Ms heart was also growing the 
hope that the study of molecular asymmetry would throw light 
on the genesis of life. To Chappuis he wrote in 1851: "... I 
have already told you that I am on the verge of mysteries, and 
that the veil which covers them is getting thinner and thinner. 
The nights seem to me too long, yet I do not complain, for I 
prepare my lectures easily, and often have five whole days a 
week that I can devote to the laboratory. I am often scolded by 
Madame Pasteur, whom I console by telling her that I shall lead 
her to posterity." 

His scientific efforts increased with the broadening of his 
hopes and illusions. He undertook a strenuous trip through 
Central Europe in order to discover the natural origin of the 
paratartaric acid to which he had owed his first scientific 

Back in Strasbourg, he used the money received from the 
Societe de Pharmacie (as a prize for his synthesis of paratar- 
taric acid) to secure additional laboratory equipment and the 
help of an assistant. His name was now widely known in chemi- 
cal circles. Academic distinctions, the Legion of Honor, and 
even a proposal on the part of some of his admirers to introduce 
his name for membership in the Academy of Sciences, were all 
indices of the wide recognition gained by his chemical studies. 
Pasteur, however, had even larger dreams. Impressed by the fact 
that only living agents can produce optically active asymmetric 
compounds, he formulated romantic hypotheses on the relation 
of molecular asymmetry to living processes, and he undertook 
bold experiments aimed at creating life anew, or modifying it by 
introducing asymmetric forces in the course of chemical re- 
actions. Thus, after ten years of disciplined work in the classical 
tradition, he had finally found a scientific outlet for his romantic 
mood. Madame Pasteur was referring to this phase of his work 
when she wrote to his father, obviously in reflection of her hus- 
band's most cherished hopes: "Louis ... is always preoccupied 
with his experiments. You know that the ones he is undertaking 
this year will give us, should they succeed, a Newton or a 


Galileo." Dumas, Blot and Ms other admirers tried in vain to 
discourage him from this search worthy of an alchemist but 
only the realization of his failure stopped him after a while, and 
he never forgot his exciting dreams. Even during the later 
crowded years, when he was involved in entirely different prob- 
lems and in passionate controversies and struggles, he was to 
accept invitations to lecture on molecular asymmetry and never 
failed to reiterate the relation which he envisioned between this 
chemical property and the processes of life. 

A combination of circumstances soon gave him the chance to di- 
rect his interest in the chemistry of life toward more attainable 
goals. In 1854, he observed that, in a solution of paratartrates in- 
fected with a mold, the "right" form of tartaric acid disappeared, 
whereas the opposite form persisted in the mother liquor. This 
revealed for the first time the close dependence of a physiological 
process in this case the destruction of tartaric acid by a micro- 
organism "upon the asymmetry of the chemical molecule. As 
Pasteur was pondering upon this extraordinary finding, a decree 
of the Minister of Public Education appointed him professor of 
chemistry and dean of science in the newly created Faculty of 
Lille with the recommendation that he center his teaching, and 
his scientific activities, on the local industrial interests. The fer- 
mentation of beet sugar for the production of alcohol was one of 
the most important industries of the region of Lille, and Pasteur 
soon started to work on the problem of alcoholic fermentation. 
Madame Pasteur wrote to her father-in-law: "Louis ... is now 
up to his neck in beet juice. He spends all his days in the distil- 
lery. He has probably told you that he teaches only one lecture 
a week; this leaves him much free time which, I assure you, he 
uses and abuses." Out of this episode came the celebrated studies 
on fermentations which brought Pasteur into intimate contact 
with the chemical phenomena of living processes, and eventually 
led him into the problems of disease. In 1857 he introduced the 
germ theory of fermentation before the Societe des Sciences of 
Lille, stating Ms belief that all transformations of organic mat- 
ter in nature would be found to be caused by various species of 


microorganisms, each adapted to the performance of a specific 
chemical reaction. 

Pasteur's conception of his responsibilities went beyond his 
own scientific interests. With the most exacting conscience and 
driving energy, he adapted his teaching to the possible applica- 
tions of chemistry to all the industries of Lille. He organized 
special laboratory demonstrations and exercises for the benefit 
of the young men who would soon pass from the university 
bench to the factory, and he arranged visits to centers of indus- 
trial activity in France and in Belgium. Within two years after 
his arrival at Lille, the scientific philosopher had been converted 
into a servant of society; and from that time on, most of his efforts 
were to be oriented, directly or indirectly, by the desire to solve 
the practical problems of his environment. 

Late in 1857 Pasteur was appointed assistant director in charge 
of scientific studies and of general administration in his old Alma 
Mater, the Ecole Normale Sup^rieure in Paris. His duties in- 
cluded the supervision of housing, boarding, medical care and 
general discipline of the students, as well as the relations between 
the school and parents and other educational establishments. He 
did not take these new responsibilities lightly, as shown by his 
reports in which he discussed, with thoroughness and vigor, 
the problems of household management, enforcement of dis- 
ciplinary measures, and reorganization of advanced studies. 

His new post did not provide him with either laboratory or 
research funds, for Balard had been replaced at the Ecole Nor- 
male by Sainte-Claire Deville, who had taken possession of the 
laboratories and of the credits allocated to the chair of chemistry. 
Undaunted by these difficulties, Pasteur found in the attic of the 
school two very small rooms abandoned to the rats, and he con- 
verted them into a laboratory which he equipped with funds 
from the family budget. The studies on alcoholic fermentation 
begun in Lille were completed in these miserable quarters. Their 
results were presented, in December 1857, before the Paris Acad- 
emy of Sciences, with the conclusion that the conversion of sugar 


into alcohol and carbon dioxide was due to the activity of yeast 
a microscopic plant. In the most emphatic terms, Pasteur stated 
that fermentation was always correlative with the life of yeast. 
Eventually, he obtained from the authorities the appointment 
of an assistant whose time was to be given entirely to investiga- 
tive work- an arrangement hitherto unheard-of. He was, fur- 
thermore, allowed to move his laboratory into a primitive "pa- 
vilion/* consisting of five small rooms on two floors, which had 
been built for the school architect and his clerks. Crowded for 
space, and deficient in funds, he improvised under the stairway 
an incubator which could be reached only by crawling on hands 
and knees. Yet it was in this uncomfortable room that Pasteur 
daily observed, for long hours, the countless flasks with which he 
convinced the world that "spontaneous generation" was a chimera. 
After a few years, the small laboratory was enlarged by addi- 
tional construction, and from these few rooms so modest by 
modem standards came the results of studies which made Pas- 
teur's name famous in many fields of learning, and a household 
word wherever civilization prevails a symbol of the benevolent 
power of science. To anyone familiar with the huge and palatial 
research institutes of today, there is a nostalgic charm in reading 
on a wall of the Rue d'Ulm, near a medallion portraying the 
master: Id jut le laboratoire de Pasteur. 

In 1860^ the Academy of Sciences awarded Pasteur its prize for 
experimental physiology, in recognition of his studies on fermen- 
tation. Nothing could have given him keener pleasure for, as 
he wrote to Chappuis and to his father, it was now his ambition 
to deal with "the mysteries of life and death." By these dramatic 
words, he implied the problem of "spontaneous generation" and 
the role of microorganisms in the transformation of organic mat- 
ter and in the causation of disease. 

Vainly had Biot and Dumas attempted to restrain Pasteur from 
entering the controversy on spontaneous generation a problem 
which they considered too complex for experimental approach. 


Pasteur persisted in his resolve, because he was convinced that 
the germ theory could not be firmly established as long as the 
belief in spontaneous generation persisted, and because he saw 
in the controversy a question of vast philosophical consequences. 
He had by then acquired such absolute confidence in his experi- 
mental skill, and was so well aware of his success as a scientific 
lecturer, that he no longer doubted his ability to deal with any 
problem, and to overcome any opposition. This complete faith 
in himself, often appearing as haughty conceit, is reflected in the 
supreme assurance with which he asserted that his results had 
final validity and were unassailable; in the scornful attacks which 
he directed at the claims of his opponents; in the way he chal- 
lenged them to scientific debates and demonstrations before 
academic committees. The studies on spontaneous generation 
brought forth the first of the famous public controversies which 
are so peculiar an aspect of his scientific life. Henceforth, each 
one of the problems that he dealt with was the occasion of ora- 
torical and literary debates in which he always triumphed over 
his opponents not only by the solidity of his facts, but also by his 
passionate vigor, and the eloquence and skill of his arguments. 
He became a crusader with an absolute belief in his creed, and 
also with an equal certainty that it was his mission to make it 

This fighting spirit was not merely a manifestation of show- 
manship, but indeed an essential part of his scientific career. In 
many cases, Pasteur devised experiments to convince the scien- 
tific public of a truth which he had reached by intuitive percep- 
tion; his most original demonstrations were often designed as 
blows to confound his adversaries. It appears best, therefore, to 
postpone until later a detailed account of these celebrated de- 
bates, as they contributed so much to the unfolding of the germ 
theory and to its introduction into the scientific consciousness 
of the nineteenth century. 

In addition to the studies on spontaneous generation and on 
the distribution of microorganisms in the atmosphere, many spec- 
tacular findings crowded Pasteur's notebooks between the years 


1860 and 1865: the discovery of butyric acid fermentation and 
of life without air, the role of yeasts and bacteria in the pro- 
duction of wine and vinegar and in the causation of their diseases; 
the demonstration that organic matter is decomposed through the 
agency of countless species of microorganisms; the teaching that 
"without the infinitely small, life would soon become impossible 
because death would be incomplete," Others before him had 
seen and described protozoa, fungi and bacteria; but it was Pas- 
teur who had most clearly the prophetic vision of their impor- 
tance in the economy of nature, and who revealed to the world 
"the infinitely great power of the infinitely small." 

Long days in the laboratory, and heated debates in scientific 
academies, were not enough to satiate Pasteur's energy. He often 
pursued his studies in the field, wherever the demands of his 
problem led him. Experiments on the distribution of germs in the 
air were carried out in the quiet air of the cellars of the Paris 
Observatoire and on high peaks in the Alps. Many of the inves- 
tigations on wines and their diseases took place at Arbois, in 
vineyard country, where a laboratory not even supplied with 
gas had first been improvised in a barroom, to the great sur- 
prise and confusion of the inhabitants and passers-by. 

He lectured to chemical societies on the subject of molecular 
structure; to the vinegar manufacturers of Orleans on the scien- 
tific basis of their trade; to the lay public on the implications of 
the germ theory and of spontaneous generation. In grave, slow, 
low-pitched voice, he conveyed to his listeners the lucidity of 
his vision, the intensity of his convictions; like his fighting spirit, 
his eloquence was part of his scientific fiber. He was as eager to 
enlighten and convince the world as he was to discover the 

Despite all his triumphs, opposition did not abate and he was 
defeated twice for election in the Academy of Sciences. Finally, 
in December 1862, he was elected as a member in the mineralogy 
section, but with only thirty-six votes out of sixty. It is said that 
when the gates of the Montparnasse Cemetery opened next day, 


a woman walked towards Blot's grave with her hands full of 
flowers. It was Madame Pasteur, who was bringing them to the 
great teacher who had lain there since February 5, 1862, and 
who had loved Pasteur with so deep an affection. Biot had given 
to the young Pasteur the sanction of his learning and intellectual 
integrity. The disciple had now become an acknowledged master, 
and was to continue enlarging the patrimony of science for thirty 
more years, achieving a fame far beyond Biot's most loving 

Nothing illustrates better the faith that some of his most dis- 
tinguished contemporaries had in Pasteur's scientific prowess than 
the odd request made to him by Dumas in 1865. A catastrophic 
disease of silkworms was then ruining the production of silk 
in the south of France. Although Pasteur knew nothing of the 
disease, and had never seen a silkworm or a mulberry tree, Dumas 
now asked him to investigate the cause of the epidemic. Equally 
astounding is the fact that Pasteur dared to accept the challenge, 
and had the stamina to work on the problem for four consecu- 
tive years under the most strenuous conditions. The practical 
control of the silkworm epidemic demanded more than scientific 
perspicacity. To make his work of value to the silkworm breed- 
ers, Pasteur had to display the qualities of a successful indus- 
trialist concerned with economic necessities as well as with the 
technical problems; he had to be always ready to meet objections, 
always willing to adapt his language and procedures to the lim- 
ited intellectual or scientific equipment of his public. 

The silkworm campaign was a magnificent initiation into the 
problems of animal diseases, and it firmly convinced Pasteur that 
epidemics could be and therefore should be conquered. However, 
several years elapsed before he entered the field of human and 
animal pathology. This delay was due in part to his hesitation in 
dealing with the technical aspects of a problem for which he had 
no training, and which was the jealously restricted domain of 
physicians and veterinarians. Furthermore, unexpected circum- 


stances forced him to limit his activity and to change for a time 
the direction of his interests. 

In 1868 Pasteur was struck by a cerebral hemorrhage which 
endangered his life and caused a permanent paralysis of the left 
arm and leg. He was just beginning to recover his health when 
the Franco-Prussian War broke out, followed by the "Commune" 
uprising in Paris. While away from his laboratory, and even 
though distraught by national disasters and by worry over his 
son in the army, he still turned in thought back to his early scien- 
tific interests. As he had done twenty years previously, he 
planned experiments to introduce asymmetric forces in the 
course of chemical reactions and of plant growth. There was still 
present in his mind the hope that, to him, would be given the 
exciting adventure of modifying the course of living processes. 

As the war ended, the immediate needs of his environment 
again took precedence over theoretical interests, and he con- 
sidered it his duty to place his knowledge at the service of French 
economy. By a somewhat pathetic choice, he resolved to improve 
the quality of French beer, in order to show that French science 
could contribute to national recovery even in a domain where the 
superiority of Germany was obvious. 

These studies on beer lasted from 1871 to 1876. With the finan- 
cial help of industry, the laboratory of the Rue d'Uhn was trans- 
formed into a small experimental brewery; personal contacts with 
French and English brewers were established, and, within a short 
time, great progress was made toward the practical goal. This 
progress did not deal specially with the improvement of the taste 
of beer, but rather with the demonstration that as had been 
found in the case of diseases of wine and vinegar the spoiling 
of beer was caused by various foreign microorganisms. With this 
understanding, it became possible to minimize contaminations 
during the manufacture of beer, and to increase the keeping 
qualities of the finished product by the technique of "pasteuriza- 

These practical findings, it appears, took little time. But Pasteur 


seized the opportunity of this new contact with the problem of 
fermentation to probe more deeply into the chemical and physio- 
logical activities of yeast; to compare them with that of other 
living cells; and to reach, thereby, profound generalizations con- 
cerning the fundamental biochemical unity of living processes. 

Once more, the natural philosopher claimed his right over the 
experimental technologist. The urge to understand nature had 
remained as pressing as the desire to answer the practical de- 
mands of society. 

A few physicians had become aware of the potential signifi- 
cance of the germ theory for the interpretation of contagious dis- 
eases and epidemics. Most prominent among them was the 
Scotch surgeon Joseph Lister, who had been inspired to introduce 
the antiseptic method in surgical operations by Pasteur's demon- 
stration of the widespread occurrence of microorganisms in the 
air. In 1873, Pasteur was elected associate member of the Paris 
Academy of Medicine, and immediately began an active partici- 
pation in its debates, never tiring of pointing out to his colleagues 
the analogy between fermentation, putrefaction, and disease. 

Medical science was then slowly approaching by a tortuous 
road a clear concept of infection, and was becoming aware of the 
part that microorganisms play in disease. In 1876 Robert Koch in 
Germany and Pasteur in France began independently the epoch- 
making investigations on anthrax from which historians date the 
germ theory of disease; their decisive experiments finally eluci- 
dated the riddle of contagion. By a prodigious effort through a 
period of ten years Pasteur established the fact that bacteria and 
filterable viruses can be the primary and sole cause of disease. 
He threw a flood of light on the mechanisms by which patho- 
genic agents spread through both animal and human communi- 
ties and bring about, in susceptible hosts, those profound dis- 
turbances of normal physiology which may eventually culminate 
in death. Even more astounding, he recognized that prior contact 
with a microscopic agent of disease can render an otherwise sus- 
ceptible host resistant to this agent; he worked out techniques by 


which the state of resistance specific immunity can safely be 
induced by first rendering the infective agent innocuous. The 
theory and the practices of immunization were applied by Pasteur 
himself to fowl cholera, anthrax, swine erysipelas and rabies, and 
they found widespread application to other diseases within his 
own time. When, in 1888, ill-health compelled him to abandon 
his tools, medical bacteriology and the sister sciences of immunol- 
ogy, public health and epidemiology had reached maturity, 
largely through his genius and devotion. 

He had not solved the problem of Me, but he had helped to 
push back the frontiers of death, and to render easier the sojourn 
of man on earth. 

The mere recital of Pasteur's scientific achievements gives only 
a feeble idea of the intensity and fullness of his life. There were 
the ignorant to enlighten, the skeptics to convince, stubborn and 
prejudiced opposition to overcome. He never shirked from a 
fight, never accepted defeat, either in the laboratory, in the acad- 
emies or in the field. He went to meet the physicians and surgeons 
in their hospitals, the veterinarians in the stables. 

To convince farmers that protection of their cattle by vaccina- 
tion was a practical possibility, he accepted, within a few months 
after the discovery of immunization, a challenge to submit his 
method to the severe test of field trial; this was at Pouilly le Fort, 
near Melun, and there in 1881 the survival of twenty-five vac- 
cinated sheep made the world conscious that medicine had en- 
tered a new era. In July and October 1885, two peasant boys 
Joseph Meister and Jean Baptiste Jupille dangerously bitten by 
mad dogs, were brought to him in the hope that he could save 
them from rabies; he accepted the mental anguish of submitting 
the two boys to his method of treatment, which without prece- 
dent in the annals of medicine, unorthodox in principle and un- 
proven in practice might have caused the death of those who 
had come to him as to a savior. Meister and Jupille survived, and 
the world went wild. 

Antirabies treatment, as we shaE see, may not be as effective 


or as practically important as was then believed; but by Ms cour- 
age, Pasteur had strengthened the faith of society in scientific 
medicine. Soon private and public funds were to low into medical 

It was not only to the promotion of his own work that Pasteur 
devoted his energies. Having recognized, with a sense of despair, 
that France was slowly losing her intellectual leadership through 
the neglect of her institutions of higher learning, he appealed to 
governmental authorities, and to the public, for the support of 
investigators and laboratories. Asked by Dumas to help in the 
preparation of a complete edition of Lavoisier's works, he under- 
took a thorough study of the great French chemist before writing 
an appreciation of his influence on the history of science. On the 
occasion of his election to the French Academy of Letters, he 
spent many days studying the philosophical faith and the life of 
Bis academic predecessor Littre, and took the occasion of the 
traditional eulogy to contrast with the exaggerated hopes of posi- 
tivist philosophy his own conviction that philosophical and reli- 
gious problems could not be analyzed by the methods of science. 
When the physiologist Claude Bernard was compelled by illness 
to abandon his studies for a year, Pasteur attempted to ease the 
forced retreat of his colleague by writing an enthusiastic account 
of Bernard's physiological and philosophical studies. Appointed 
professor of physics and chemistry at the School of Fine Arts, he 
refused to deal lightly with the subject. Instead, he prepared for 
his students critical analyses of the relation of architectural de- 
sign to human comfort and health, scholarly accounts of the bear- 
ing of chemical knowledge on the practices of oil painting, and 
simple experiments to illustrate the properties of different oil 

The exacting thoroughness which governed his behavior in the 
laboratory also characterized his participation in the affairs of 
the community. Unlike Faraday, who withdrew from the world 
to devote all his genius and energy to experimental science, and 
unlike most scientists, who abandon experimentation as soon as 
other responsibilities become too pressing, Pasteur managed to 


remain faithful to the laboratory while serving society. He was 
both a fervent scientist and an effective citizen. 

National and personal tragedies brought into relief the full- 
blooded quality of his temperament He had the narrowness and 
the exaltation of the patriot. The bombardment of Paris, and in 
particular of the Museum of Natural History, by the Prussians in 
1871 inspired him to return, with words of anger and contempt, 
the honorary degree that he had received from the University of 
Bonn. Proud as he was of the glorious traditions of his country, 
he knew well that the France of the 1870's was no longer the 
leader of European thought which she had been in the eighteenth 
century. And yet, while he looked with envy and marvel at the 
vigor of civilization beyond the French borders, he retained un- 
altered his romantic attachment to his country: he always spoke 
of France with the same tender words that he used when speak- 
ing of his family. 

Just as he had suffered in his patriotic affection, so he felt 
deeply the losses which bereaved his family. In 1865, while he 
was working on silkworm diseases in Alais, he received a tele- 
gram announcing that his father was very ill. He immediately 
started for Arbois, but arrived too late to see for one last time 
the man who had been his inspiration, his confidant, his guiding 
star the symbol of family and country, of affection and duty. 
That night Pasteur, then forty-three years old, wrote to his wife 
from the old home where his character had been formed: 


Grandfather is no more; we have taken him this morning 
to his last resting place, close to little Jeanne's. In the midst 
of my grief I have felt thankful that our little girl had been 
buried there. . . . Until the last moment, I hoped I should 
see him again, embrace him for a last time . . . but when 
I arrived at the station, I saw some of our cousins aE in 
black, coming from Salins; it was then that I understood 
that I could but accompany him to the grave. 

He died on the day of your first communion, dear C<cile; 
those two memories will remain in your heart, my poor 
child. I had a presentiment of it when, that very morning, 


at the Iiour when he was struck down, I was asking you to 
pray for the grandfather at Arbois. Your prayers will have 
been acceptable unto God, and perhaps the dear grand- 
father himself knew of them and rejoiced with dear little 
Jeanne over Cecile's piety. 

I have been thinking all day of the marks of affection I 
have had from my father. For thirty years I have been his 
constant care; I owe everything to him. When I was young, 
he kept me from bad company and instilled into me the 
habit of working and the example of the most loyal and best- 
filled life. He was far above his position both in mind and 
in character. . . . You did not know him, dear Marie, at the 
time when he and my mother were working so hard for 
the children they loved, for me especially, whose books and 
schooling cost so much. . . . And the touching part of his 
affection for me is that it never was mixed with ambition. 
You remember that he would have been pleased to see me 
the headmaster of Arbois College? He foresaw that advance- 
ment would mean hard work, perhaps detrimental to my 
health. And yet I am sure that some of the success in my 
scientific career must have filled him with joy and pride; 
his son! his name! the child he had guided and cherished! 
My dear father, how thankful I am that I could give you 
some satisfaction! 

Farewell, .dear Marie, dear children. We shall often talk 
of grandfather. How glad I am that he saw you all again 
a short time ago, and that he lived to know little Camille. 
I long to see you all, but must go back to Alais, for my 
studies would be retarded by a year if I could not spend a 
few days there now. 

In this letter appears Pasteur's profound sentimentality, in 
which familial love, religious belief and sense of duty are so in- 
extricably associated. But in the last sentence is also revealed 
another dominant aspect of his personality: the will to work and 
the urge to create, that no sorrow and no handicap could over- 
come, He had ignored the most extreme material difficulties in 
his garret at the Ecole Normale; he also ignored physical infir- 
mity when he became partially paralyzed in 1868. 

As soon as he began to regain his faculties, a week after the 
attack of paralysis, he dictated a scientific communication to his 


student Gernez, who was watching over Mm during the night. 
Within a few weeks, he started again for Aiais to resume his 
studies on silkworm diseases, despite the difficulties of the trip, the 
lack of comfort of his southern quarters, and contrary to the ad- 
vice of his physicians. For Pasteur was before all a man of in- 
domitable will. It was not only his opponents that he wanted to 
overpower; it was also nature it was himself. He was an ad- 
venturer and a conqueror, but one whose goal was to serve the 
inner God the "enthusiasm'* from which originate all great 
human actions. He had hoped that the mysteries of Hfe and death 
would be revealed to him at the end of his journey. But, failing 
this romantic goal, there were still worth-while lands to discover 
and to conquer. In 1888, as he opened the new research institute 
to be called after him, he dedicated it with the following words: 

**. . . Two contrary laws seem to be wrestling with each other 
nowadays: the one, a law of blood and of death, ever imagining 
new means of destruction and forcing nations to be constantly 
ready for the battlefield the other, a law of peace, work and 
health, ever evolving new means for delivering man from the 
scourges which beset him." 

It was to serve peace, work and health that he had labored, 
fought and suffered with so much passion. 

Pasteur's first published work dates from 1847, the last one 
from 1892; thus for almost half a century, the dauntless warrior 
had been before the scientific world, tirelessly working at the 
solution of theoretical and practical problems. 

By 1885, he was an immensely famous man, honored by acad- 
emies, entertained by princely and democratic rulers, acclaimed 
by specialists. But it was the antirabies treatment which assured 
his place in the heart of all civilized men, which made of him a 
hero in the golden legend of science. Within a short time after 
the treatment of Meister and Jupille an international subscription 
was opened to accumulate funds for the creation in Paris of an 
institute devoted to the treatment of rabies, and to the prosecution 
of microbiological and biochemical research. Of this building, 


Pasteur could say that "every stone of it is the material sign of a 
generous thought. All virtues have co-operated to raise this 
dwelling of labor." 

On December 27, 1892, Bis seventieth anniversary was the oc- 
casion of a solemn jubilee in the great amphitheater of the Sor- 
bonne, attended by the President of the French Republic and 
by delegations of French and foreign institutions of learning. As 
emphasized by one of the official orators, it was not merely a 
great scientist who was the hero of the day, but a man who had 
devoted all his strength, his heart and his genius to the service 
of mankind. 

". . . Who can now say how much man owes to you and how 
much more he wiU owe to you in the future? The day will come 
when another Lucretius will sing, in a new poem on Nature, 
the immortal Master whose genius engendered such benefits. 

"He will not describe him as a solitary, unfeeling man, like the 
hero of the Latin poet; but he will show him mingling with the 
life of his time, with the joys and trials of his country, dividing 
his life between the stern enjoyment of scientific research and the 
sweet communion of family intercourse . ." 

Unable to speak for emotion, and compelled to extend his 
thanks through the voice of his son, Pasteur then expressed for a 
last time in public his conviction that science would some day 
bring happiness to man. 

". . . Delegates from foreign nations, who have come from so 
far to give France a proof of sympathy: you bring me the deepest 
joy that can be felt by a man whose invincible belief is that 
Science and Peace will triumph over Ignorance and War, that 
nations will unite, not to destroy, but to build, and that the future 
will belong to those who will have done most for suffering 

Addressing the students, he recalled the rich satisfactions which 
he had derived from his years of toil and expressed his undying 
confidence in the power of the experimental method to improve 
the lot of man on earth. 



This is my testament: 

I leave to my wife everything that the law allows me to 
leave her. May my children never depart from the line of 
duty and always retain for their mother the love that she 

Paris, March 29, 1877 
Arbois August 25, 1880 


"Young men, have faith in those powerful and safe methods, 
of which we do not yet know all the secrets. And, whatever your 
career may be, do not let yourselves be discouraged by the sad- 
ness of certain hours which pass over nations. Live in the serene 
peace of laboratories and libraries. . . ." 

Now, his strength was gone. He entered his new Institute an 
ill and exhausted man, broken by time and by endless toil. He 
had still a few years to live. To anyone else, these might have 
brought the happiness of well-deserved rest and recognition, re- 
ward of a rich and productive life. The microbiological sciences 
which he had done so much to create were growing before his 
eyes; the great Institute which bore his name was a humming 
hive of research and an international center of learning; honors 
came to him from everywhere and a happy family surrounded his 
leisurely days. But how empty was his life now that scientific 
creation was no longer permitted him! How tragic the vision of 
the passionate adventurer and conqueror, now armed with the 
material means that he had lacked in the past, his mind still clear, 
his dreams still living, but his body too weak to start again on the 
endless trail! 

On November 1, 1894, he was seized with a violent attack of 
uremia from which he only partially recovered. On the following 
New Year's Day, he could enjoy in the laboratories of the Pasteur 
Institute a display, especially prepared for him, of the flasks, 
cultures and other specimens, companions of his celebrated 
studies. The bacilli of diphtheria and of bubonic plague re- 
cently isolated were also on exhibition as symbols of the mag- 
nification of his own work. His interest in science was still alive, 
also his patriotic fervor. When asked if he would accept from the 
German Emperor the badge of the Order of Merit, he refused. 
He had not forgotten 1871. The old fiery heart was still burning. 

On June 13 he left Paris for a period of recovery at a branch of 
the Pasteur Institute at Villeneuve FEtang, in the park of Saint- 
Cloud. For a few weeks, he could continue his dreams under the 
noble trees of the park, surrounded by his family and disciples. 


Rapidly, however, Ms paralysis and weakness increased; his 
speech became more and more difficult. It is reported that on 
September 27, as he was offered a cup o milk, he refused it with 
the words: "I cannot" These were his last words. For the first 
time, he yielded; not to obstacles, not to opposition, not to men 
only to a power greater than man, to the Death which he had 
fought with all Ms genius and all Ms heart. The next day, Septem- 
ber 28, 1895, in the late afternoon, he died, his body almost en- 
tirely paralyzed, one of his hands in that of his wife, the other 
holding a crucifix. 

The monastic simplicity of the room in wMch he passed away 
is an expression of the austerity of his life; and the gorgeously 
adorned chapel, in wMch his tomb was set, a symbol of the place 
that he occupies in the memory of men. 


Pasteur in Action 

The painter or draughtsman should be solitary, so 
that physical comfort may not injure the thriving of 
the mind, especially when he is occupied with the 
observations and considerations which ever offer them- 
selves to his eye and provide material to be treasured 
up by the memory. If you are alone, you belong 
wholly to yourself; and if you are accompanied even 
by one companion, you belong only half to yourself; 
and if you are with several of them, you will be ever 
more subject to such inconveniences. 


SPEAKING at the unveiling of Jean Baptiste Dumas's statue in 
1889, Pasteur contrasted the rich life of his revered master with 
that of the scientists who keep aloof from the social implications 
of their activities: 

"Among superior men, there are those who, isolating themselves 
in their studies, have for the public turmoil of ideas only disdain, 
pity and indulgent condescension. Unconcerned with the general 
public opinion, they aim at exerting a direct influence only on 
narrow, selected circles. Should this elite fail them, they still find 
in the spectacle of their own intelligence an acute and lasting 
pleasure. . . . 

"There are a few men who are equally at ease in silent labor 
and in the debates of the large assemblies. Above and beyond 
their personal investigations, which assure them a special place 
in posterity, they keep their minds attentive to all general ideas, 
and their hearts open to generous sentiments. These men are the 
guides and protectors of nations. . . . 



"Still others, finally, carried away by the eagerness to see their 
ideals triumph, throw themselves into the straggles of public 
Pasteur probably thought of himself in pronouncing these 
words. He had labored in the silence and solitude of libraries 
and laboratories, but he had also shared the practical problems 
of his time in the shops and in the fields, fighting whenever neces- 
sary at the tribunes of academies, in the technical press and be- 
fore the lay public. Like Dumas he had been a great scientist, a 
great teacher, but also an effective man of action and organizer. 
Unlike him, however, and unlike most scientists who abandon the 
laboratory bench when the call of administrative responsibilities 
becomes urgent, he did not pass successively through these dif- 
ferent phases; he lived all of them at the same time. Single- 
handed, he could carry a given problem from the level of abstract 
concept, through the exacting discipline of the experimental 
method, to the hustle and bustle of practical life. The whole of 
science was his province its dreams, discipline, controversies, 
struggles, triumphs, and practical realizations. Home and the 
market place, as well as laboratories and academies, saw him 
function in all the expressions of the scientific way of life. This 
was perhaps the most characteristic aspect of his genius. 

For many years, he worked alone. When, later, young men 
came to join him, they participated in the execution of his work, 
but rarely contributed to the elaboration of his thoughts. He often 
left his assistants completely ignorant of the strategy of his in- 
vestigations, revealing to them only the part essential to the task 
of the day. "He kept us remote from his thoughts," said Duclaux, 
his most intimate student and associate, who also spoke of "the 
Olympian silence with which he loved to surround himself until 
the day when his work appeared to him ripe for publicity. He 
said not a word about it, even in the laboratory, where his assist- 
ants saw only the exterior and the skeleton of his experiments, 
without any of the life which animated them. 


"Very briefly, without unnecessary explanation, Pasteur would 
indicate to each his task and send him away to attend to his 

Loir, who was Pasteur's technical assistant from 1884 to 1888, 
has recently confirmed Duclaux's account. "He wanted to be alone 
in his laboratory and never spoke of the goal he had in mind. 
Pondering over his notebooks, he would write on small cards the 
experiments that he wanted to have done and then, without ex- 
plaining anything, would ask his assistants ... to do them/' 

Even during the periods of greatest activity, there were but 
few assistants; each had his room, or his corner in the main labo- 
ratory, where he worked in silence, without disturbing the master 
except when called upon for discussion. When Bertin became 
director of sciences at the Ecole Normale, he urged Pasteur to 
study the effect of physical agents on the activity of micro- 
organisms. Pasteur appeared interested and Bertin appointed the 
young physicist Joubert as assistant. Soon, however, Joubert had 
to handle a Pravaz syringe to share in the work of the laboratory. 
As this was outside his own line of interest, he left, to be replaced 
by other young physicists also introduced by Bertin. Several came 
in and soon left, discouraged by the little interest that Pasteur 
took in their presence. For Pasteur, the choice of a collaborator 
was a matter of little concern, in fact a very secondary thing. 
There had to be one, since the position was open; but who it was 
mattered little, provided he did faithfully and in silence the work 
which was asked of him. 

Pasteur's meditations could proceed only in silence, and the 
presence of any visitor foreign to his occupations was sufficient to 
disturb him; only persons working on his problems were welcome 
in the laboratory. Once when he had gone to visit Wurtz at the 
School of Medicine, he found the chemist at work amidst his 
pupils, in a room full of activity, like a humming beehive. "How/* 
exclaimed Pasteur, "can you work in the midst of such agitation?*' 
"It excites my ideas," answered Wurtz. "It would put mine to 
flight," retorted Pasteur. 

The laboratory was opened to very few and one could pene- 


trate it only by ringing the bell at the main door. Pasteur was not 
cordial even to his friends when he was at work; to interrupt him 
was to make him unhappy. "I can still see him/* wrote Roux, 
"turning toward the intruder, waving his hand as if to dismiss 
him, and saying in a despairing voice, *No, not now, I am too 
busy/ And yet, he was the most simple and most hospitable of 
men; but lie could not understand how anyone could dare to 
disturb a scientist at work on his notes. When Chamberland and 
I were in the course of an interesting experiment, he would watch 
around us, and seeing from far through the window our friends 
coming to fetch us, he would meet them himself at the door to 
send them away/' 

He was not eager to accept physicians in his laboratory, even 
during that period when he was engaged in medical research. He 
felt that the demands upon them were too varied to allow them 
to focus attention on specific problems, and to achieve the con- 
centration essential to investigative work. He was irritated also 
by the trend in medical circles at that time to discuss any sub- 
ject in florid and eloquent language, instead of by the factual 
statements of experimental science. Moreover, "Physicians are 
inclined to engage in hasty generalizations. Possessing a natural 
or acquired distinction, endowed with a quick intelligence, an 
elegant and facile conversation . . . the more eminent they 
are . . . the less leisure they have for investigative work. . . . 
Eager for knowledge . . . they are apt to accept too readily at- 
tractive but inadequately proven theories." 

Physicians may interpret this statement as a manifestation of 
inferiority complex on the part of the chemist toward the art of 
medicine. In reality, it merely expresses the traditional feud be- 
tween investigator and practitioner. Claude Bernard, although 
trained in the Paris School of Medicine during its period of great- 
est clinical glory, shared Pasteur's irritation at his medical col- 
leagues. Have you noticed, he would say, how physicians, when 
walking into a room, always carry about themselves an air that 
seems to imply "Look at me, I have just saved another life"? This 
was in the middle of the nineteenth century. Today Pasteur and 


Bernard might find material for their scorn in the scientist who, 
unmindful of the long history of the world prior to his efforts, 
entertains the illusion that his last experiment will open a new era 
in thought 

Pasteur did not want the hustle and bustle of medical life to 
disturb the peace of his laboratory. He had arranged for the 
clinical aspects of the work on rabies, administered by Dr. 
Grancher, to be carried out in an annex a few blocks away from 
the Ecole Normale, and he saw to it that the casual interest of 
the medical visitor should not introduce confusion in the disci- 
plined and meditative atmosphere of his sanctuary. He was ex- 
tremely shocked at learning from Loir that Grancher's laboratory 
had two fine armchairs, one of them a rocking chair. "Pasteur 
could not understand that one could feel the need of physical 
comforts in a laboratory. It confirmed his conviction that he 
should keep his own quarters closed to people with such ideas/' 
Even smoking was an unwelcome dissipation, that could be in- 
dulged in by Pasteur's assistants only while he was away. 

Silence was especially imperative while the master was formu- 
lating the next phase of his experiments his "working hypoth- 
eses." For days he would then absorb himself in the study of his 
notebooks, remaining isolated from everybody and everything, 
ignoring the presence of his collaborators, and not even raising 
his head for hours in succession. Thus he could recapture from 
his past experience the immense wealth of observations and im- 
aginative thoughts recorded in the tidy pages crowded with his 
small writing. From them would emerge those fragments which 
attracted and held as in a field magnetized by the intensity of his 
thoughts organized themselves into new and unexpected pat- 

When he had completed the study of his notes, the new phase 
would begin. Now he would construct the tentative plot of his 
next scientific story the "working hypothesis," from which 
would be born the project of the next experiment At that time, 
he would pace the floor for hours without speaking; he would 


even continue Ms silent monologues at home, walking back and 
forth from one room to the other. These solitary meditations 
lasted for days. During that period he was so absorbed in his 
thoughts that he was unaware of the presence of persons around 
him. Duclaux often had to wait long hours before being asked 
the object of his visit Anyone who had to bring up an urgent 
matter found it necessary to insist in order to force his attention. 
Then he reacted as if waking out of a dream, but never with im- 
patience; he slowly turned toward the interrupter, passing his 
hand over his face several times in a familiar gesture. 

After his ideas had taken shape, he re-established contact with 
his collaborators, telling them only enough of his dreams, goals 
and plans to formulate the technical details of the experiments. 
Exploratory tests were few in number, but designed with extreme 
care to determine whether the hypothesis had a factual founda- 
tion. If the results were negative, the tentative ideas were imme- 
diately rejected from his mind, and it became useless to bring 
them back to his attention; he would not even remember them. 
If, on the contrary, positive results suggested that the hypothesis 
might be valid, experiments were tirelessly multiplied to explore 
and develop its possibilities. 

Experiments were usually carried out as soon as they had been 
sufficiently discussed and prepared. This rapid passage from 
conception to execution accounts, in part, for Pasteur's phe- 
nomenal scientific productivity. He was never discouraged by 
obstacles, a quality that he regarded as one of his greatest as- 
sets "Let me tell you the secret which has led me to the goal. 
My only strength resides in my tenacity** a judgment which has 
been confirmed by Roux: "How many times, in the presence of 
unforeseen difficulties, when we could not imagine how to get 
out of them, have I heard Pasteur tell us, 'Let us do the same 
experiment over again; the essential is not to leave the subject.' " 

The unmatched reproducibility of Pasteur's findings either 
of the period when he worked alone or after paralysis forced him 
to delegate the execution of his experiments to others is suffi- 


cient evidence of the precision of Ms work. He was not, however, 
much interested in laboratory techniques as such, but demanded 
only that they be well adapted to answer his questions, to settle 
the truth of his hypotheses, and to permit the formulation of 
effective and dependable procedures. Above aU, the answer must 
be unequivocal, for he wanted to be able "everywhere and always 
to give the justification of principles and the proof of dis- 

Most of his experiments were simple in design and execution, 
but all details were carried out, observed and recorded with the 
most exacting attention. The loving care with which he prepared 
and handled crystals of organic substances for the studies on 
molecular structure becomes the more impressive when it is real- 
ized that all measurement of the angles of the crystalline facets, 
and of the deflection of optical activity, had to be carried out with 
homemade instruments. The isolation, transfer, and cultivation 
of microbial cultures had to be done without the benefit of bacte- 
riological equipment; autoclaves did not exist; the use of gelatin 
and agar plates had not yet been introduced; an incubator had 
to be improvised in a corner of the stairway. Although many of 
Pasteur's conclusions rested on microscopic studies, he used only 
the most simple techniques and equipment to familiarize himself 
with the microbial world. All cultures were examined directly in 
the living state until 1884, when stains and the oil immersion lens 
were introduced into his laboratory from Germany. Nevertheless, 
with his primitive means of observation, and without any prior 
training in biological microscopy, Pasteur recognized new species 
of microorganisms, differentiated their physiological states, and 
could diagnose diseases of vinegar, wine and beer, as well as of 
man and animals, with an accuracy unexcelled at the time. 

When his attack of paralysis in 1868 deprived him of the use 
of his left hand he had to depend upon assistants for the perform- 
ance of most of his experiments. Himself a masterful laboratory 
worker, he was very exacting of others. On hearing his assistants 
point out that an experiment he wanted to have done presented 


special difficulties, lie would say: "It is your responsibility; ar- 
range it anyway you like, provided it is done, and well done." The 
description left by Loir shows with what care he supervised 
the technical phases of his work. 

"At the time of transferring cultures, Pasteur and I went to the 
incubator with a small tray for transporting the flasks. They were 
brought to a special, small room which was never opened on any 
other occasion and they were kept there for exactly two hours in 
order to allow them to reach room temperature undisturbed. 
After that time had elapsed, we returned to the small room, still 
without speaking and with a minimum of motion. I sat at the table 
and Pasteur sat on a chair behind me, a little to the side and two 
feet behind, in order to be able to see everything I did. On the 
table was placed a wire basket containing long, sealed sterile 
pipettes. I took one, broke the tip, flamed it ... before using it 
for inoculation. The platinum wire x did not come in use in the 
laboratory until 1886." 

Like the performance of the experiment, the observation of 
results was a ritual of which no detail could be slighted. "It is 
necessary to have seen Pasteur at his microscope/' Roux said, "to 
form an idea of the patience with which he could examine a 
preparation. In fact, he looked at everything with the same minute 
care. Nothing escaped his nearsighted eye; and jokingly, we used 
to say that he could see the microbes grow in his bouillons.** 

Long hours of silent observation were also devoted to the in- 
fected animals, their surroundings, and their behavior. He would 
stand in a corner of the basement (where the animals were kept) 
with a card in his hand, watching for hours the motions and atti- 
tudes of an infected chicken. If perchance anyone should go down 
without knowing that the master was already there, he would 
signal to remain silent, and continue his observations. 

Then back at his small desk he would stand, writing everything 
he had observed. He demanded of his collaborators an exact ac- 
count of their own phase of the work, asking for the most minute 

1 Loops made of platinum wire are now often used instead of glass 
pipettes for the transfer of bacterial cultures. 


details; he insisted on writing down, himself, all available infor- 
mation, as if to make more completely Ms own part of his very 
flesh and mind everything pertaining to the work. "He did not 
leave to anyone the responsibility of keeping the laboratory note- 
book tip-to-date. He himself took down the information that we 
gave him, in all its details. How many pages he thus covered, with 
small irregular and crowded handwriting, with drawings in the 
margins, side and footnotes, the whole entangled and difficult to 
read for anyone not used to it, and yet kept with extraordinary 
care. Nothing was written down that had not been duly observed, 
but once it was written, it became for Pasteur an incontestable 
truth. When, during a discussion, he would bring the argument 
It is in the notebook/ no one would dare to discuss the problem 

"Once the notes were taken, we would discuss the experiments 
to be undertaken, Pasteur standing at his desk, ready to write 
down what would be agreed upon, Chamberland and I facing 
him, leaning against a cabinet. This was the important time of 
the day; each would give his opinions, and often an idea at first 
confused would be clarified by the discussion and lead to one of 
those experiments which dissipate all doubts. At times we dis- 
agreed and the voices would be raised; but although Pasteur was 
regarded as opinionated, one could express one's mind to him; 
I have never seen him resist a reasonable opinion. 

"A little before noon, someone came to call Pasteur for lunch; 
at half -past twelve he returned to the laboratory and, usually, we 
found him motionless near a cage, observing a guinea pig or a 
rabbit. Around 2 P.M. Madame Pasteur sent for him, as he 
would otherwise forget the meetings of academies and committees 
of which he was a member. , . . He returned around 5 P.M., 
wanted to be informed immediately of what had been done, took 
down notes on it and verified the labels of the experiments. Then, 
he would report on the most interesting papers heard at the 
Academy and would discuss the work in progress." 

It is this extreme devotion to all the details of the work, this 
complete knowledge and mastery of all the facts pertaining to 


his experiments, which gave Pasteur such absolute confidence in 
his own results and assured their reproducibiMty in all cases. Be- 
cause of this confidence, he never hesitated to challenge his op- 
ponents before academic commissions, as he knew that he could 
always duplicate his results; because of it also, he accepted the 
incredibly drastic terms of the public test on the vaccination of 
sheep against anthrax "What succeeded with fourteen sheep in 
the laboratory will succeed just as well with fifty at Melun." And 
it did not only in Melun, but wherever his detailed instructions 
were followed to the letter, not only in the case of anthrax vac- 
cination, but in all cases where investigators had enough energy, 
patience and loving care to respect in all their details the instruc- 
tions issued from the infallible notebooks. 

The investigation into fermentations brought Pasteur into con- 
tact with the practical world and he soon developed an acute 
awareness of the power of the scientific method in increasing the 
effectiveness of technological operations. He did not share the 
common belief that pure science and applied science correspond 
to two independent forms of intellectual activity, demanding dif- 
ferent gifts from those engaging in them. He felt that sound train- 
ing in the theoretical disciplines was an adequate preparation for 
the task of giving scientific findings practical application, and 
expressed these views on many occasions for example, in a 
letter written in 1863 to discuss the organization of professional 

There are no applied sciences . . . There are only . . . 
the applications of science, and this is a very different 
matter. . . . 

. . . We must place professional teaching in the hands 
of professors as well trained as possible in the theory, prin- 
ciples and methods of pure science, but of whom we shall 
ask, in addition, that they show an interest in the applica- 
tions of science. Is it possible rapidly to procure professors 
with these qualifications without resorting to expensive 

. . . Yes, certainly, because the study of the applications 


of science is easy to anyone who is master of the theory 
of it, ... 

The studies on beer, started in a brewery near Clermont- 
Ferrand after the Franco-Prussian War, were continued in Paris. 
There a pilot plant was established in the laboratory of the Rue 
d'Ulm. Chemical studies went on in the large room of the ground 
floor, while boilers and fermentation vats crowded the basement. 
The austere atmosphere of the laboratory was mellowed for a 
time by the aroma of fermenting barley and hops, while on the 
days of degustation the clinking of glasses and the laughter of 
Bertin (who acted as expert beer taster) dispelled the atmosphere 
of silence of the sanctuary. 

Much of the work on vinegar and wine was carried out in 
Orleans and at Arbois in direct contact with producers. The tech- 
nical development of pasteurization required many consultations 
with them to make sure that the degree of heating was not such as 
to spoil the taste of the product, and with engineers in order to 
work out the practical aspects of the method. Pasteur's publica- 
tions on the subject present detailed specifications with drawings 
of equipment for carrying out pasteurization on an industrial 
scale. He did not neglect to consider the cost of operation and to 
discuss other economic aspects of the preservation of foods and 
beverages by heating. 

In order to study the diseases of silkworms Pasteur trained 
himself, his assistants and even his family, in the practical opera- 
tions involved in the production of silk. He was not satisfied with 
establishing only the scientific validity of the egg-selection 
method; he wanted also to prove that it was practically feasible 
and economically profitable. For several months every year be- 
tween 1866 and 1870 he behaved as if he were the director of a 
commercial enterprise and sent his assistants all over the south of 
France to teach his method to the silkworm breeders. 

The vaccination against anthrax and swine erysipelas brought 
forth responsibilities similar to those of the control of silkworm 
diseases. To meet the cost of experimentation with farm animals, 


it was necessary to enlist the interest and support of govern- 
mental bodies and agricultural societies. The laboratory was 
moved to farm or pasture whenever the problem called for 
studies in the field. For the first time, bacteriological research was 
being carried out on a large scale as a part of national economy. 
The commercial production and distribution of the vaccine was 
turned over to Chamberland, who established an annex of Pas- 
teur's laboratory at Rue Vauquelin close to the Ecole Normale. 
It was not easy to convince skeptics that vaccination was a profit- 
able operation because it entailed the risk of a few animals dying 
following the injection of the attenuated vaccine. Pasteur pro- 
posed the organization of an insurance company to protect farm- 
ers against unavoidable losses, and thus help in overcoming their 

After 1875, the experimental brewery in the cellar of the labo- 
ratory was dismantled to be replaced by a small animal house 
and hospital, for the study of contagious diseases. With the initia- 
tion of the work on rabies larger animals' quarters became neces- 
sary but they were not easy to secure, as everywhere the public 
was terrified at the thought of rabid dogs being housed in the 
vicinity of residential dwellings. Finally, however, large kennels 
were established at Garches, in a former state domain close to 
the park of Saint-Cloud. 

The successful outcome of Meister's and Jupille's treatment 
brought about a sudden demand for immunization of persons 
bitten by rabid animals. The preparation of the rabies vaccine, 
the treatment of patients, the collection and analysis of statistical 
evidence, all received Pasteur's personal supervision. Makeshift 
arrangements had to be improvised for the maintenance of large 
numbers of rabbits and for the desiccation of the infected spinal 
cords of rabbits used in the preparation of the vaccine. The medi- 
cal administration of the new treatment for which there was no 
precedent required difficult decisions. The housing of patients 
arriving from all parts of the world, often without adequate re- 
sources, presented unexpected problems which were solved by 
emergency measures. 


"Many/* wrote Duclaux, "have described the strange spectacle 
offered by the laboratory and the courtyard near to it, where as- 
sembled a picturesque and polyglot crowd of bitten individuals 
come to beg of science the end of their apprehensions and the cer- 
tainty of tomorrow. But what has not been mentioned enough is 
the contagious confidence which spread through all the new- 
comers and made of them believers whose faith contributed to 
their recovery. 

"Laboratory and consultation room soon became too small; we 
had to leave the hospitable Rue d'Ulm to establish ourselves on 
larger grounds borrowed from the former College Rollin. It was 
while we were camped there that the international subscription 
was opened which resulted in the creation of the Pasteur In- 

The Institute was organized to provide more extensive facilities 
for the treatment of rabies and also for the prosecution of 
microbiological, biochemical and physiological sciences. Pasteur's 
dream of large research laboratories with adequate resources for 
investigation had finally come true, but as he entered the mag- 
nificent institute, his strength failed him; he was "a man van- 
quished by time." Yet he continued to haunt the laboratories, 
following with eagerness the work of his disciples. He was a 
symbol of the great creators who, despite poverty and at the cost 
of sacrifices and suffering, establish the foundations of science 
that less gifted men may continue to add slowly to the great 
structure arising from the struggles of genius. 

Theoretical studies in the laboratory and practical tests in the 
field were not sufficient to satisfy Pasteur's eagerness to prove 
the validity of his convictions. He acknowledged three steps in the 
establishment of evidence: first to try "to convince oneself . . . 
then to convince others ... the third, probably less useful, but 
very enjoyable, which consists in convincing one's adversaries." 
As a vigorous fighter, he derived great satisfaction from over- 
coming his opponents. Because he believed in the importance of 


Ms work, lie was eager to see it known and accepted everywhere, 
and was often unwilling to wait for the judgment of time. 

His discoveries and observations were quickly reported through 
brief communications to learned societies and in letters to his 
masters and colleagues. In addition, he carried his message to 
the world in the form of polished and formal lectures to scientific 
academies, as well as to technical and lay audiences. In limpid, 
forceful and at times eloquent language, he summarized on these 
occasions his experimental studies, and also their philosophical 
and practical implications. 

He wrote long and detailed letters to clarify public opinion on 
matters which he considered of importance, to defend his work 
and his viewpoints, also to educate his followers as well as his 
opponents in theoretical principles and technical procedures. 
These letters were to individuals and to the press, and he often 
elected this latter channel to publicize the application of his 

For example, he reported in a trade journal the manner in 
which he convinced the Mayor of Volnay, M. Boillot, of the 
effectiveness of controlled heating as a means of preserving 

I beg the Society to allow me to publish my interview ... in 
dialogue form. The teachings to be derived from this conversa- 
tion will thus reach more effectively those who could profit by 
them. . . 

PASTEUR: Do you heat your wines, M. Mayor? 

M. BOILLOT: No, sir ... I have been told that heating 
may affect unfavorably the taste of our great wines. 

PASTEUB: Yes, I know. In fact, it has been said that to heat 
these wines is equivalent to an amputation. Will you be 
good enough, M. Mayor, to follow me in my experimental 
cellar . . . ? Here are rows of bottles of your great vintages 
which have been heated, and there, bottles of the same 
vintages not heated. The comparative experiment dates from 
1866, more than seven years ago . . . 


[For two pages, Pasteur describes in great detail how the 
mayor, after tasting heated and unheated wines, had to acknowl- 
edge the superior keeping quality of the former, even in the case 
of the products from his own vineyards.] 

M . BOILLOT: I am overwhelmed, I have the same impres- 
sion as if I were seeing you pouring gold into our country. 

PASTEUK: There you are, my dear countrymen, busy with 
politics, elections, superficial reading of newspapers, but 
neglecting the serious books which deal with matters of im- 
portance to the welfare of the country, indeed to your own 
interests. I suppose you consider it might demand too much 
effort to understand and follow the wise advice of those who 
labor on your behalf, often at the sacrifice of their own 

M. BOILLOT: Do not be mistaken, sir. I had read in the 
Proceedings of the Academy that your process preserves and 
improves our wines, but I have read also on the following 
page the statement by some of your colleagues that heating 
can spoil the flavor. How do you expect us, poor vintners, 
to decide? 

PASTEUR: . . . You are revealing there one of the bad 
traits of our national character. . . . Our first inclination is 
to doubt the success of others. And yet, M. Mayor, had you 
read with attention, you could have recognized that every- 
thing I wrote was based on precise facts, official reports, de- 
gustation by the most competent experts, whereas my op- 
ponents had nothing to offer but assertions without proof. 

M. BOELLOT: . . . Do not worry, sir. From now on, I shall 
no longer believe those who contradict you and I shall at- 
tend to the matter of heating the wines as soon as I return 
to Volnay . . . 

Even more peculiar to Pasteur were the passionate and cele- 
brated controversies which because of his vitality, his convic- 
tion and his genius gave such a picturesque and often dramatic 
flavor to the heroic age of microbiology. In subsequent chapters, 
we shall consider in detail the controversies on problems of theo- 
retical interest with Liebig on the germ theory of fermentation; 
with Pouchet and Bastian on spontaneous generation; with 
Claude Bernard and Berthelot on the intimate mechanisms of 


alcoholic fermentation; with Colin on anthrax of chickens; with 
Koch on the efficacy of anthrax vaccination; with Peter on the 
treatment of rabies. There were also conflicts involving priority 
rights, or those arising simply from the clash of incompatible 
personalities. Whatever the cause of the argument, scientific or 
personal, Pasteur handled with the same passion those whom 
he believed to misrepresent truth, or to be prejudiced against 

When young, he communicated his feelings to the members of 
his family. Thus at the occasion of his first defeat for election to 
the Paris Academy of Sciences he wrote to his wife of his con- 
tempt for the "mediocrities who control the election/* looking 
forward to the day when he could "read before them a fine mem- 
oir while thinking: Fools that you are, try to do as well. ... I 

am now speaking of that fool of and of and of so many 

other nonentities who have arrived where they are only because 
there was no one else, or by sheer luck." 

In 1862, as his name was presented to the Academy for the 
third time, attempts were made in certain groups to minimize the 
significance of his studies on tartaric acids. The situation was 
critical as the vote was expected to be close. Duclaux's account 
of Pasteur's immediate reaction will serve to introduce this "spirit 
of combativity which constitutes one of the facets, and not the 
least curious, of his scientific temperament." 

"That evening there was to be a meeting of the Societe Philo- 
mathique where it was likely that many important scientists would 
be present. ... I was dispatched to a cabinetmaker and came 
back with screws, files and a long block of pine lumber. It was 
ten years since M. Pasteur had touched the problem of the 
tartrates, but he still had their crystalline forms at his finger tips. 
A few strokes of the saw, guided by him with a marvelous surety, 
sufficed to transform the lumber into a series of crystalline forms 
with their faces and facets . . . which were rendered more read- 
ily distinguishable being covered with different colored papers. 

"His exposition began as a lesson . . , But in ending, M. Pas- 


teur challenged Ms contradictors to confess their ignorance, or 
their bad faith . . . telling them, in essence, If you understood 
the question, where is your conscience? And if you did not under- 
stand it, how did you dare speak of it?' M. Pasteur has since won 
many oratorical victories, but I know of none better deserved 
than the one gained by this penetrating improvisation. He was 
still in ebullition as we walked toward the Rue d'Ulm, and I re- 
member making him laugh by asking him why ... he had not 
thrown his wooden crystals at the heads of his opponents." 

Pasteur became more and more inflammable as time went on. 
Not satisfied with challenging his opponents to disprove his 
claims, he heaped scorn upon their ignorance, their lack of ex- 
perimental skill, their obtuseness or even their insincerity. From 
his desk at the Academy of Medicine, he pointed out to clinicians 
the emptiness of their debates, the uncertainties of their premises 
and conclusions, and contrasted the vagueness of the clinical art 
with the assured power of the new physiological and micro- 
biological sciences. In sentences which often betrayed an irritat- 
ing haughtiness under their outward pretense of humility, he 
lectured to physicians on the germ theory of fermentation, its 
application to putrefaction, gangrene and contagious disease, and 
the "fruitful fields of the future" which it opened to medicine. 
He told the verbose and facile clinician Poggiale, his colleague 
at the Academy of Medicine: "I refuse the right to verify, ques- 
tion or interpret my findings ... to anyone who is satisfied with 
reading my studies in a superficial manner, his feet at the fire- 
place." To those who, like Colin, misunderstood or misapplied 
the principles of the experimental method, he scornfully pointed 
out that one single positive finding of his was worth more than 
a hundred negative experiments. "M. Colin," he told the Academy, 
'looks into 98 obscure closets and concludes from this that light 
is not shining outside." Or again, "There is only one road which 
leads to truth, and one hundred that lead to error; M. Colin al- 
ways takes one of the latter." 

When he despaired of convincing his colleagues of the Acad- 


emy, he would address, over their heads, the young physicians 
and students who attended the meetings; 

<0 Young men who . . . are perhaps the medical future of our 
country, do not come here to be entertained by the excitement 
of polemics, but to learn of methods. Know then, that I denounce 
as an example of the most detestable of methods the reasoning 
which leads M. Colin to conclude from a negative observation 
that there exists in the inoculation material of anthrax a virulence 
factor other than the bacteria . . . 

"I denounce as a reasoning worthy of a Moliere comedy, of 
Moliere ridiculing the medical spirit of his time, the following 
paragraph from one of M. Colin's replies. f l do not know ex- 
actly what the anthrax bacteria are. It is not absolutely sure that 
they are living beings. ... Is it impossible that they are of the 
same origin as the anatomical structures . . . ?* " 

Irritated by the tendency of his colleagues to trust in argument 
and eloquence rather than in the accurate statement of facts, he 
even dared lecture the Academy of Medicine as a body on the 
proper manner of conducting scientific debates. 

"You were asking yourself how the Academy could intro- 
duce . . . the true scientific spirit in its works and discussions. 
Let me give you a method which would not be a panacea but 
which certainly would be useful. We should resolve never to 
call this desk a tribune, or a communication presented from it 
a discourse, or the one who is speaking an orator. Let us leave 
these expressions to political assemblies, deliberating on topics 
which do not lend themselves to factual demonstration. These 
three words tribune, discourse, orator appear to me incom- 
patible with scientific rigor and simplicity.** 

Roux has described the intensity with which Pasteur reacted 
to the famous discussions on the germ theory of disease, which 
took place in the Paris Academy of Medicine. 

"He would leave the meetings in a great state of emotion. 
M. Vallery-Radot, Chamberland and I often waited for him as 


he came out. 'Have you heard them! To experiments they reply 
only by speeches/ he would say. His irritation slowly subsided 
as we walked home; and he imagined further experiments, to 
bring more light, for contradictions excited him to new inves- 
tigations * . . 

"Pasteur's passion for science sometimes carried him to con- 
clusions of an amusing naivety. For him, a man guilty of a bad 
experiment or of unsound reasoning could not be trusted in any 
way. Once when he was reading to us in the laboratory a piece 
of work which he considered particularly bad, he exclaimed with 
irritation: *I should not be surprised if a man capable of writing 
such nonsense should beat his wife/ 2 As if conjugal cruelty were 
the utmost in scientific misbehavior/' 

He was aware of his lack of serenity, and sometimes spoke of 
this "lively and caustic manner . . . which I recognize to be 
peculiar to me in the defense of truth." "Moderation! This is a 
word which is rarely applied to me. Yet, I am the most hesitating 
of men, the most fearful of committing myself when I lack evi- 
dence. But on the contrary, no consideration can keep me from 
defending what I hold as true when I can rely on solid scientific 
proof/' Once more at the occasion of his jubilee in 1892, he as- 
sured his colleagues: "If I have at times disturbed the calm of 
your academies by discussions of too great an intensity, it is 
only because I wanted to defend the cause of truth." Pasteur has 
been criticized for the violence of his attacks on the enemies of 
the germ theory. It must be remembered, however, that he was 
fighting almost singlehanded against the official doctrines of the 
day. Darwin was fortunate in having for his disciple such a master 
of exposition as Huxley, The latter constituted himself "Darwin's 
bulldog," and just as Darwin's motto was peace at any price, so 
Huxley's was war, whatever the cost. In contrast, Pasteur was 
for a long time almost the only articulate champion of the germ 
theory, and he had to act both Darwin's and Huxley's roles. 

# * # 

2 Another account reads "should be untrue to his wife." 


The defense of his own discoveries was not the only cause 
which excited his fighting spirit; science, and its contribution to 
the welfare of mankind and to the power of the nation, inspired 
some of his most passionate tirades. Shocked at the neglect of 
scientific research in France, he attempted to capture the interest 
of governmental bodies, by letters and by affixing to his studies 
dedications to sovereigns, by lectures and demonstrations de- 
signed to entertain as well as instruct the court and society. Be- 
cause he respected traditional and legal authority, it was with 
expressions of reverence, and almost humility, that he first 
pleaded the cause of science. His words and person were shown 
polite interest, but when no action was forthcoming in answer to 
his request for funds while millions of francs were spent on 
the new Paris Opera House, and not even a few thousand could 
be found for laboratories he lost patience. Much as he had ap- 
pealed to the young physicians from his desk at the Academy, he 
decided to appeal directly to public opinion by sending to the 
official newspaper Le Moniteur an impassioned plea for the sup- 
port of scientific research. The article was rejected by the editorial 
committee as subversive, but was finally published in the Revue 
des Cours Scientifiques in 1868 under the title Le budget de la 
science. In the meantime, it had reached the Emperor, who 
was sufficiently moved by it to take immediate and personal ac- 
tion for the reorganization of French science; but the Franco- 
Prussian War soon interrupted the execution of the new plans. 

Pasteur saw in the defeat of France a tragic vindication of his 
attitude, and in 1871 reissued his warning in an enlarged form, 
under the title Quelques reflexions sur la science en France. In it, 
he lamented the material circumstances which prevented young 
French scholars from devoting their energies to investigation; 
he contrasted the miserable state of laboratories in France with 
the magnificent support they were receiving abroad and particu- 
larly in Germany; he recalled the prominent part played by 
French science in allowing the country to overcome the onslaught 
of Europe during the Revolution and the Napoleonic wars. 

"The public bodies, in France, have long ignored the correla- 


tion between theoretical science and the life of nations. Victim 
of her political instability, France has done little to maintain, 
spread, and develop, the progress of sciences. . . . She has lived 
on her past, believing herself great through the discoveries of 
science, because of the material prosperity which she owed to 
tihem, but failing to realize that she was allowing the sources of 
wealth to go dry. 

'While Germany multiplied her universities, created a healthy 
competition between them, surrounded her teachers and doctors 
with honor and consideration, organized vast laboratories with 
the best equipment, France, enervated by revolutions, always 
preoccupied with the sterile search for the best form of govern- 
ment, paid only distant attention to her institutions of higher 

"In the present state of modern civilization, the cultivation of 
the highest forms of science is perhaps necessary even more to 
the moral state of a nation than to its material prosperity. . . . 

"Our disasters of 1870 are present in the mind of everyone. . . . 
It is too obvious, unfortunately, that we lacked men adequately 
prepared to organize and utilize the immense resources of the 
nation . . . 

"If, at the moment of the supreme peril, France could not find 
the men to take advantage of her power and of the courage of 
her children, it is, I am certain, because she has neglected the 
great labors of thought for half a century, particularly in the 
exact sciences/* 

He described with enthusiasm how, by virtue of her leader- 
ship in scientific research during the fifty years before the first 
Revolution, the France of 1792 had multiplied her forces through 
the genius of invention and had found, wherever needed, men 
capable of organizing victory. And in words of overwhelming 
conviction he exclaimed, "Oh my country! You who so long held 
the scepter of thought, why did you neglect your noblest crea- 
tions? They are the divine torch which illuminates the world, 
the live source of the highest sentiments, which keep us from 
sacrificing everything to material satisfactions. . . . 


'Take interest, I beseech you, in those sacred institutions which 
we designate tinder the expressive name of laboratories. Demand 
that they be multiplied and adorned; they are the temples of 
wealth and of the future. There it is that humanity grows, be- 
comes stronger and better. There it learns to read in the works 
of nature, symbols of progress and of universal harmony, whereas 
the works of mankind are too often those of fanaticism and de- 
struction . . ." 

Pasteur carried home his scientific preoccupations, and his 
family was witness to his silent meditations, audience to his 
dreams. As we have seen, this intimate association between the 
home and the life of study had begun during childhood with 
his parents. In the Pasteur family, learning was not a passing 
phase, to be disposed of as soon as possible in order to enjoy 
an idle summer vacation or devote the leisure of adulthood to 
trivial chat and the reading of the daily newspaper; learning was 
a never-ending component of one's life, changing not in intensity 
with the seasons and the years, but only as to its nature accord- 
ing to one's social responsibilities and place in the world. 

In order to be closer to his work Pasteur and, whenever pos- 
sible, his assistants had their living quarters near the laboratory. 
The working day began at 8 A.M., lasted until 6 P.M., and holi- 
days were rare. "I would consider it a bad deed," said he, "to let 
one day go without working." Evenings were devoted to reading, 
correspondence, and the preparation of scientific papers. Madame 
Pasteur copied everything "with her beautiful handwriting, so 
easy to read." Never did a manuscript go to the printer except 
in the neatest form, with all amendments carefully pasted in, 

Pasteur carried into social and home life mannerisms which 
grew out of his scientific problems. As much as possible he 
avoided shaking hands, for fear of infection. At the dinner table 
he would wipe glassware and dinnerware in the hope of removing 
contaminating dirt. Loir has described the odd behavior that 
arose from his habit of intense and detailed observation. 


"He minutely inspected the bread that was served to him and 
placed on the tablecloth everything he found in it: small frag- 
ments of wool, of roaches, of flour worms. Often I tried to find 
in my own piece of bread from the same loaf the objects found 
by Pasteur, but could not discover anything. All the others ate 
the same bread without finding anything in it. This search took 
place at almost every meal and is perhaps the most extraordinary 
memory that I have kept of Pasteur/' 

During periods of great preoccupation, he remained completely 
silent even with members of his family. Nothing could erase the 
tenseness of his expression until he had solved his problem. Once 
the solution had been found, however, he became exuberant, and 
wanted everyone around him to share his hopes and joy; wife 
and children had to participate in both his anguish and his tri- 
umph. He would pursue at mealtime his controversies of the 
afternoon at the Academy, or with some distant opponent. To 
him, it was inconceivable that a subject worthy of intense dis- 
cussion at a scientific meeting should not remain the center of 
attention at a social gathering. 

Pasteur's only masters were Work and Science. In truth, he 
could tell the musicians and artists assembled to honor his 
Jubilee in 1892 that he was seeing them all for the first time; 
and he was sincere when he wrote, "Let us work, this is the only 
thing which is entertaining." What were the motives which pow- 
ered this incessant activity, this dedication to a liTe of toil, this 
sacrifice of the small pleasures of existence? 

One hears now and then that Pasteur was avid for money, 
that a desire for fortune motivated his enormous expenditure of 
energy. As a small French bourgeois, issuing from an environ- 
ment of struggle, he certainly longed for financial security; but 
so do most men. There is, however, no evidence that the urge for 
money played a significant role in directing his activities. After 
he had developed techniques for the preservation of vinegar, wine 
and beer by the use of heat, he took patents to protect the rights 
to his discovery. That there were discussions within his family 


concerning the possible financial exploitation of these patents is 
revealed in one of his letters; "My wife . . . who worries con- 
cerning the future of our children, gives me good reasons for 
overcoming my scruples.'* Nevertheless, Pasteur decided to re- 
lease his patents to the public, and did not derive financial profit 
even from the development or sale of industrial equipment de- 
vised for pasteurization. 

The discovery of immunization against anthrax and swine ery- 
sipelas again presented the opportunity of large monetary re- 
wards. Following the Pouilly le Fort experiment, Pasteur had 
turned over to his laboratory the profits coming from the sale of 
the anthrax vaccine in France, reserving for himself and his col- 
laborators only the income from the sale to foreign countries. 
In 1882 a Dutch financier offered him one hundred thousand 
francs, a large sum at the time, for the exclusive right to use the 
technique in South Africa. Pasteur contemplated accepting the 
offer, and began to dream with his family and close associates 
of the use he would make of this fortune. However, a word of 
caution from Dumas, pointing out the disgraceful manner in 
which Liebig had allowed his name to be used as an advertise- 
ment for meat extract, sufficed to stop him, and he went no 
further with his plan. 

The practice was common in France for one individual to hold 
several major teaching appointments in order to increase his 
income. Pasteur strongly objected to this, as interfering with in- 
vestigative work; true to his own preaching, he gave up in 1868 
the post of professor of physics and chemistry at the School of 
Fine Arts, which he had held for three years, and he refused to 
teach chemistry at the Ecole Normale while he held the chair at 
the Sorbonne. 

According to Loir, there had been many discussions concerning 
the advisability of using the manufacture and sale of vaccines as 
a source of income for the laboratory. This policy was finally 
adopted under Duclaux's influence and against Pasteur's judg- 
ment in order to facilitate the financing of further scientific work. 
In fact, Pasteur willingly left to others the management of aff airs 


whenever money was involved, and his own salary was paid di- 
rectly to his wife. His daily needs were small; the laboratory 
and afternoon meetings at the Academy bounded his life out- 
side of his home. When on a scientific trip, he took just enough 
money to meet the immediate necessities and depended on 
his wife to supply him with further funds when the need 

It is, indeed, incredible that the mere urge for money could 
have been the incentive for the expenditure of so much energy 
and talent, and only small men with empty hearts and without 
imagination could explain Pasteur's ambitions in such simple 
terms. At the most, financial independence was the expression 
of security and even more a symbol of the place which he con- 
sidered his due in society. Official decorum and the proper type 
of carriage for important occasions were, for him as was neat 
and conservative clothing more a matter of decency than of 
comfort or enjoyment. Like most creative workers, he respected 
the traditions and conventions which lay outside the field of his 
own endeavor, probably because he lacked the time to reassess 
their meaning and value, and because he was too conscientious 
to formulate lightly a personal code of ethics. He certainly had 
social ambitions, but not so much to participate in the brilliant 
and entertaining life of his time as to be recognized as a leader 
of his community, in fact as the most elevated expression of its 
genius. He once said, "Cities should be aware that they are re- 
membered in the course of ages only through the genius or the 
valor of a few of their children." He wanted to be one of those 
for whom cities are remembered. 

He was jealous of his right to his discoveries. Once, very early 
in his career, when he had hurried publication for fear of losing 
priority, he wrote with candor: 

"How disturbing to lose by hasty publication the charm of 
following a fruitful idea with calm and prolonged meditation! 
And yet I would be even more disturbed if M. Marbach . . . 
should arrive first at the general idea which I follow. 


"I therefore incline toward the immediate publication of all 
the positive facts I know." 

In later years, he combatted with endless evidence and argu- 
ment the accusation that he had borrowed ideas or facts from 

Concern for priority is undoubtedly one of the most sensitive 
points among scientific workers. Thus Humphry Davy, who had 
refused to patent his discovery of the miners* safety lamp, or to 
receive money for it, became very angiy at the assertion that 
Stephenson deserved priority for the invention. And yet, most 
scientists are unwilling to acknowledge this jealousy, and pre- 
tend that their only interest is in the advancement of science 
irrespective of recognition. Pasteur has spared us from these false 
claims because he did not know how to conceal the great pride 
he took in his discoveries, as well as in the honors poured upon 
him by his scientific peers, by his country, by the world. For 
him, social recognition was the symbol that he had fulfilled his 
calling. The longing to transcend the primary needs and satisfac- 
tions of one's vegetative life, to become one of the greatest actors 
in the unfolding of the future of one's community or of humanity, 
is an urge probably widespread among men. In this sense, it is 
true that many great achievements are motivated by generous im- 
pulses and that the acknowledgment of it by society is often a 
source of gratification to aspiring men. Pasteur differed from most 
of them only by displaying in public, often with a childish naivete, 
the pleasure which he derived from fame. 

He always attributed his eagerness for achievement and for 
recognition to a desire to brighten the glory of France. His 
patriotism was strengthened by the memory of the glorious 
past of his country, as we have seen, and also by his aware- 
ness that France had lost the leading position she had occu- 
pied in Europe during the preceding century. This identification 
between personal urges and national glory had been instilled 
into him by his father, who had never forgotten the intoxi- 
cating days when the flags of Revolutionary and Imperial 


France waved over the capitals of Europe. Speaking of him, 
Pasteur once evoked the influence of this atmosphere on his own 
life. "I still can see you reading by the lamp after the day of 
labor some account of battle from one of those books of con- 
temporary history which recalled the glorious era of which you 
had been witness. While teaching me to read, you were careful 
to make me aware of the greatness of France/' And he was cer- 
tainly sincere when he asserted: "Science has been the dominating 
passion of my life. I have lived only for it and the thought of 
France supported my courage during the difficult hours which 
are an inevitable part of prolonged efforts. I associated her great- 
ness with the greatness of science." When, following the French 
disasters of 1870-1871, he was offered by the Italian Government 
a chair of chemistry at the University of Pisa, with a high salary 
and very great personal advantages, after much hesitation he 
refused. "I should feel like a deserter if I sought, away from my 
country in distress, a material situation better than that which 
it can offer me." 

Granted that love of country and urge for social recognition 
can serve as stimuli to human endeavor, they are of little impor- 
tance in deciding the direction of one's efforts. And, in fact, the 
one problem in which the desire to serve his country was the 
most direct motivation of Pasteur's choice, namely the improve- 
ment of French beer, was also the most trivial. The book which 
crowned this phase of his work, the Studies on Beer, reveals Pas- 
teur's attitude. It contains little concerning brewing practice ex- 
cept information related to the microbial alterations of beer; 
but it discusses at great length problems which had been very 
close to his heart for many years the distribution of micro- 
organisms in nature and the mechanism of fermentation. 

Indeed, Pasteur knew well that real science is of equal rele- 
vance to all men, whatever their nationality. It is true that the 
scientist, as a citizen, can add to the fame of his community by 
the distinction of his achievements. Few, however, are the cases 
where national pride alone appears as an adequate inducement 
to scientific pursuit. 


"I am imbued with two deep impressions; the first, that science 
knows no country; the second, which seems to contradict the 
first, although it is in reality a direct consequence of it, that 
science is the highest personification of the nation. Science knows 
no country because knowledge belongs to humanity, and is the 
torch which illuminates the world. Science is the highest per- 
sonification of the nation because that nation will remain the first 
which carries the furthest the works of thought and intelligence. 

"The conviction of having attained truth is one of the greatest 
joys permitted to man, and the thought of having contributed to 
the honor of one's country renders this joy even deeper. If science 
knows no country, the scientist has one, and it is to his country 
that he must dedicate the influence that his works may exert in 
the world." 

Although Pasteur spoke now and then of the disinterested 
search for truth, he had only little hope that science would ever 
reveal the ultimate nature of things. He regarded science as an 
instrument of conquest which permitted man to gain mastery 
over the physical world, rather than as a technique for under- 
standing the universe. Repeatedly, he expressed gratification at 
seeing that his labor would help to better the lot of man on earth. 
"To him who devotes his life to science, nothing can give more 
happiness than increasing the number of discoveries, but his cup 
of joy is full when the results of his studies immediately find 
practical applications." 

On many occasions, also, he stated in terms of unquestionable 
warmth and sincerity his desire to alleviate the sufferings of his 
fellow men. "One does not ask of one who suffers: What is your 
country and what is your religion? One merely says: You suffer, 
this is enough for me: you belong to me and I shall help you." 

And at the occasion of his jubilee, he summarized his creed by 
the oft-quoted words: 

"I am utterly convinced that Science and Peace will triumph 
over Ignorance and War, that nations will eventually unite not 
to destroy but to edify, and that the future will belong to those 


who have dojie the most for the sake of suffering humanity." 
He believed that great was the "part played by the heart in 
the progress of sciences" and indeed, there is no question that 
the desire to be useful to his fellow men, his awareness of the 
problems of his community, determined to a large extent the fields 
of endeavor in which he gained his greatest popular triumphs. 
By natural endowment and training, he was qualified to pursue 
far and profitably the theoretical problems which had occupied 
his younger years and which haunted the rest of his days. In- 
stead, he chose to devote much of his energy to the practical 
affairs of man. By so doing, he did not consider that he was sac- 
rificing intellectual distinction. For, according to him, the search 
for knowledge which has direct bearing on the practical problems 
of human life could not be readily differentiated from the search 
for abstract truth. 

Among theoretical scientists, there are those who pretend that 
the desire to contribute to human welfare plays no part in the 
motivation of their efforts. They regard pure curiosity, or at the 
most some concern with the dignity of the human mind, as suffi- 
cient to explain and justify the pursuit of science for its own 
sake. By so doing, they place their activities above the level of 
the ordinary preoccupations of their fellow men, an attitude 
which gives them the illusion of occupying an exalted place in 
the social structure. It is probable that conceit or blindness, rather 
than intellectual superiority, is often the true inspiration of this 
philosophy, for social pressure exerts a greater influence on the 
orientation of their activities than most scientists are willing to 

Nevertheless, there certainly exists a curiosity to understand 
the universe and the significance of life, which is independent 
of the immediate needs of society, and which accounts for much 
intellectual exertion. It is this longing which the English biologist 
Joseph Arthur Thomson expressed in the following words. "The 
scientific worker has elected primarily to know, not do. He does 
not directly seek, like the practical man, to realize the ideal of 
exploiting nature and controlling life; he seeks rather to idealize 


to conceptualize the real, or at least those aspects of reality 
that are available in his experience . . " In fact, as we have seen, 
Pasteur's passionate engrossment with research began long before 
he could visualize his scientific efforts as having a direct effect 
on the welfare of mankind. None of his subsequent achievements 
gave him greater emotional pleasure than did the discovery of a 
correlation between optical activity and the morphology of the 
tartaric acid crystals. 

The act of discovery, independent of its consequences, re- 
mained for Pasteur a never-ending enchantment: enchantment 
arising from the emotion associated with treading over land here- 
tofore unknown to man; enchantment from the new vistas sud- 
denly opened to the discoverer, and the promise of more adven- 

"It is characteristic of science and of progress that they con- 
tinuously open new fields to our vision. When moving forward 
toward the discovery of the unknown, the scientist is like a trav- 
eler who reaches higher and higher summits from which he sees 
in the distance new countries to explore." 

Pasteur often returned to his earlier publications. Turning the 
pages of his writings, he would marvel at the lands that he had 
revealed by dispelling the fogs of ignorance and by overcoming 
stubbornness. He would live again his exciting voyages, as he told 
Loir in a dreamy voice: "How beautiful, how beautiful! And to 
think that I did it all. I had forgotten it" 

These had been the great adventures of his life. If he spoke 
of laboratories in endearing terms, if he demanded that they be 
adorned, it was not only because he saw in them the temples of 
the future, but also because he had known happiness and en- 
chantment within their walls. 

Whatever the initial motivation of his efforts idle curiosity 
or social compulsion; whatever the target at which he aims 
discovery of a natural law or solution of a practical problem the 
scientist of genius perceives the far-reaching implications of the 


isolated facts which come within his field of vision, and recognizes 
between them relations of broad generality. Pasteur exhibited 
from the beginning of his scientific career, and retained through- 
out his life, this ability to recognize large theoretical issues, to 
the extent of translating practical achievements into the terms of 
general laws of nature. From simple observations on the optical 
activity of tartrates he derived an interpretation which encom- 
passed the problem of molecular structure. The study of wine 
and beer led him to see in the life of yeast a microcosm illustrat- 
ing the biochemical unity of life; while studying fowl cholera he 
discovered the principles of immunization and the broader fact 
that any animal coming into contact with a foreign substance 
becomes indelibly altered by this experience. 

The eagerness to control nature for practical ends, and the 
longing to conceptualize, were always simultaneously present in 
his mind. The fact that both tendencies remained equally power- 
ful throughout his life constitutes perhaps the most characteristic 
trait of his scientific career, and accounts for its somewhat erratic 
course. Moreover, there grew very early, deep in his heart, the 
secret desire to accomplish some prodigious feat. The ever-recur- 
ring evocation of his early studies on the optical activity of organic 
molecules, with its possible bearing on the genesis of life, sup- 
ports the view that practical problems never completely monopo- 
lized his mind. Speaking of the late afternoon conversations in 
the laboratory, Roux has stated that Pasteur's imagination reached 
its highest peak whenever these early studies were mentioned. 
"He would speak in poetical terms of molecular asymmetry and 
of its relation to the asymmetric forces of nature. On these 
days, Pasteur forgot the dinner hour; Madame Pasteur had to 
have him called several times, or had to come herself to fetch 

By reason of his very success as an experimenter, he became 
the prisoner, almost the slave, of limited and practical tasks. But 
beyond the daily problems, his gaze was fixed on the romantic 
hope that he would some day penetrate the secret of life. The 


alchemist never entirely ceased to live and function within the 

By upbringing, schooling and self-discipline, Pasteur was made 
to behave as a bourgeois and to accept the rigid code of experi- 
mental science; but he was by temperament an adventurer. With 
so many worlds to conquer, others yet to be discovered and even 
more to imagine, why invoke money or social distinction to ac- 
count for his labors? Rewards and honors of all sorts came to him, 
and he enjoyed them. But how pale they must have been, com- 
pared with the glowing visions of insight, divination, adven- 
ture and power which he experienced at the Ecole Normale and 
under the trees of the Luxembourg Gardens, in the company of 
ghosts of so many other dreamers! 


From Crystals to Life 

The men of experiment are like the ant; they only 
collect and use: the reasoners resemble spiders, 
who make cobwebs out of their own substance. But 
the bee takes a middle course, it gathers its mate- 
rial from the flowers of the garden and of the field, 
but transforms and digests it by a power of its 


PASTEUK spent the first ten years of his scientific life, from 1847 
to 1857, investigating the ability of organic substances to rotate 
the plane of polarized light, and studying the relation of this 
property to crystal structure and molecular configuration. These 
studies provided the basis on which the new science of stereo- 
chemistry was built during his own lifetime. From them also arose 
his intuitive belief that fermentations are the manifestations of 
living processes, a belief that eventually led him to the germ 
theory of fermentation and of disease. There is no indication that 
Pasteur entered the field of crystallography in the hope of solv- 
ing great theoretical or practical problems of physics, chemistry 
or biology. As a serious student he was eager to participate in 
the investigations of some of his respected teachers and to follow 
the line of their interests. The problem that was to be of such 
momentous consequence for his career, for the future of chemi- 
cal and biological sciences, and for the welfare of society was 
the outcome of the personal associations which he enjoyed while 
a student at the Ecole Normale. 
At the beginning of the century Jean Baptiste Biot, who was 


soon to play such an important role in Pasteur's life, had recog- 
nized that crystals of quartz rotate the plane of polarized light, 
traversing them in the direction of their long axis. He had also 
noticed that certain quartz crystals rotate light to the right, 
whereas others of the same thickness rotate light to the same 
extent to the left. At about the same period, Haiiy and his pupil 
Delafosse had observed on quartz some crystal faces called 
hemihedral facets which were inclined in one di- 
rection, sometimes in the other, with reference to the edges of the 
crystal that bore them. It was the English astronomer John 
Herschel who had the idea of combining the purely crystallo- 
graphic observations of Haiiy and Delafosse on the existence of 
right- and left-handed facets in quartz crystals with the physical 
observations of Biot on right- and left-handed rotation of light 
by the same crystals. He was able to establish that the ability 
of quartz to rotate the plane of polarized light is an expression of 
the configuration of the crystal. 

It was well known that quartz exhibits its characteristic effect 
on light only when in the crystalline state. In 1815, Biot had dis- 
covered that certain natural organic substances such as sugar, 
camphor, tartaric acid, oil of turpentine, protein, and the like 
could also rotate the plane of light but that, in contrast with 
quartz, they exhibited their optical activity in the liquid state and 
in solution. 

Pasteur was well acquainted with all these facts as his pro- 
fessor of mineralogy at the Ecole Normale was the same Dela- 
fosse who had made a special study of the facets present on the 
quartz crystals. Another accidental association further increased 
his familiarity with the problem of the relation of optical activity 
to crystalline structure. At the end of 1846, there came to work 
in Balard's laboratory, where Pasteur was now an assistant, a 
young and intense chemist Auguste Laurent whose direct 
influence on the eager student can be traced in a manuscript 
note left by Pasteur. 

**. . . One day it happened that M. Laurent studying, if I 
mistake not, some tungstate of soda, perfectly crystallized- 


showed me, through the microscope, that this salt, apparently 
very pure, was evidently a mixture of three distinct kinds of 
crystals, easily recognizable with a little experience of crystal- 
line forms. The lessons of our modest and excellent professor of 
mineralogy, M. Delafosse, had long since made me love crystal- 
lography; so, in order to acquire skill in using the goniometer, 
I began to study carefully the formations of a very fine series of 
compounds, all very easily crystallized; tartaric acid and the 
tartrates. . . . Another motive urged me to prefer the study of 
those particular forms. M. de la Provostaye had just published 
an almost complete work concerning them; this allowed me to 
compare, as I went along, my own observations with those, al- 
ways so precise, of that clever scientist." 

Thus, it appeared as if fate had brought together many in- 
fluences to prepare Pasteur for his first scientific adventure. He 
had become attracted by the "subtle and delicate techniques 
involved in the study of these charming crystalline forms"; in- 
fluenced by HerscheFs observations and by his association with 
Delafosse and Laurent, he had in mind constantly the relation 
between optical activity and the orientation of facets in quartz 
crystals; finally he had become very familiar with the optical 
activity of tartrates and with their crystalline characteristics. 
Although he knew that the optical activity of organic substances 
was an expression of the molecule in solution, and not of the 
crystalline structure as in the case of quartz, he assumed, prob- 
ably under the influence of Delafosse, that there might be some- 
thing external for example, facets in the tartrate crystals 
which would indicate the arrangement of the atoms within the 
tartrate molecule. 

As he was pondering over these facts, Biot communicated to 
the Academy of Sciences in 1844 a note in which the German 
chemist, Mitscherlich, described some very curious findings 
which startled Pasteur and launched him on that voyage of dis- 
covery which was thereafter coextensive with his life. 

Two different forms of tartaric acid were then recognized. 


One, the true tartaric acid, had long been known to occur as a 
constant component of tartar in the wine fermentation vats. 
The other, Brst seen in 1820 by Kestner, an industrialist of Thann, 
occurred among the large crystals of true tartaric acid in the form 
of needlelike tufts which resembled oxalic acid crystals. It had 
been called "paratartaric acid/' also "racemic acid,** to recall its 
origin from the grape (racemus}* Mitscherlich had discovered 
that the two forms of tartaric acids and their respective salts, the 
tartrates and paratartrates, "have tihe same chemical composition, 
the same crystal shape with the same angles, the same specific 
gravity, the same double refraction, and therefore the same angles 
between their optical axes. Their aqueous solutions have the same 
refraction. But the solution of the tartrate rotates the plane of 
polarization, while the paratartrate is inactive." 

Pasteur saw immediately an incompatibility between the find- 
ing that the two tartrates behaved differently toward polarized 
light, and Mitscherlich's claim that they were identical in every 
other particular. He was convinced that there had to be some 
chemical difference between the two substances, and he hoped 
that this difference would express itself in the shape of the 
crystals. This incompatibility provided him with the first specific 
question, the first well-defined problem, on which to test his skill 
as an experimenter. In so doing, he demonstrated one of the 
most fundamental characteristics of the gifted experimenter: 
the ability to recognize an important problem, and to formulate 
it in terms amenable to experimentation. 

Imbued with the idea that optical activity must be associated 
with irregularities in the crystalline shape, Pasteur began a sys- 
tematic observation of the crystals of tartaric acid and of the 
various tartrates which he had laboriously prepared. He saw at 
once on the tartrate crystals small facets, similar to those present 
on quartz crystals, which had escaped the attention of his prede- 
cessors a telling example of the part played by a working hy- 
pothesis in the process of discovery. Acute observers as they were, 
Mitscherlich and de la Provostaye had failed to see the small 
facets on the tartaric acid crystals because they were not inter- 


ested in seeing them. Pasteur, on the contrary, looked for them 
because he had postulated their existence, and he detected them 
at once. So do preconceived ideas influence our perception of 
natural phenomena as they do our judgment of economic, social 
and moral problems. 

The nineteen tartrates prepared and studied by Pasteur were 
found to exhibit the typical facets on one side of their crystals 
and all rotated polarized light in the same direction. He nat- 
urally inferred that crystal shape and optical activity were linked 
in the case of tartrates as they were already known to be in the 
case of quartz, notwithstanding the fundamental difference that 
quartz possesses optical activity only in the crystalline state, 
whereas the tartrates retain this property in solution. To clinch 
the correlation, it was now necessary to determine whether the 
crystals of paratartaric acid, found by Mitscherlich to be optically 
inactive, differed from the optically active tartrates either in not 
possessing any facets at all or in having symmetrical pairs of 
facets. To this end, Pasteur set about examining the crystals of 
paratartaric acid and its salts and found, in accordance with his 
anticipations, that they did not possess the facets characteristic 
of the true tartrates. 

Mitscherlich had made his allegation with respect to one par- 
ticular substance, namely the sodium-ammonium paratartrate, 
and Pasteur therefore examined it with especial care. To his 
intense surprise and disappointment, and quite contrary to antici- 
pation in the light of his hypothesis, he found facets similar to 
those present on the crystals of optically active tartrates. Still 
intent on finding a difference, he noticed that while the facets 
were all turned towards the right in the tartrate, in the case of 
paratartrate crystals some were turned to the right, and some to 
the left. Obeying the promptings of his hypothesis, he sedulously 
picked out the right-handed crystals and placed them in one 
heap, and the left-handed crystals in another, dissolved each 
group in water, and then examined the two solutions separately 
in the polarimeter with results which made of this simple opera- 
tion one of the classical experiments of chemical science. The 


solution of the right-handed crystals turned the plane of polariza- 
tion to the right, the solution of the left-handed crystals to the 
left. When the two solutions were mixed in equal amounts, the 
mixture proved optically inert. 

It is easy to recapture the dramatic quality of the situation and 
the intense excitement which it must have caused in the young 
investigator. Pasteur was so overcome with emotion by his finding 
that he rushed from the laboratory, and, meeting one of the chem- 
istry assistants in the hall, embraced him, exclaiming, "I have just 
made a great discovery. ... I am so happy that I am shaking 
all over and am unable to set my eyes again to the polarimeterr 

Pasteur retained throughout his life a vivid memory of this 
first scientific triumph and never tired of referring to it in con- 
versations and in lectures. As late as 1883, almost forty years after 
the event, he described it again in the course of a lecture deliv- 
ered before the Societe Chimique de Paris. 

"I was a student at the Ecole Normale Superieure, from 1843 
to 1846. Chance made me read in the school library a note of the 
learned crystallographer, Mitscherlich, related to two salts: the 
tartrate and the paratartrate of sodium and ammonium. I medi- 
tated for a long time upon this note; it disturbed my schoolboy 
thoughts. I could not understand that two substances could be 
as similar as claimed by Mitscherlich, without being completely 
identical. To know how to wonder and question is the first step 
of the mind toward discovery. 

"Hardly graduated from the Ecole Normale, I planned to pre- 
pare a long series of crystals, with the purpose of studying their 
shapes. I selected tartaric acid and its salts, as well as paratartaric 
acid, for the following reasons. The crystals of all these substances 
are as beautiful as they are easy to prepare. On the other hand, 
I could constantly control the accuracy of my determinations by 
referring to the memoir of an able and very precise physicist, 
M. de la Provostaye, who had published an extensive crystallo- 
graphic study of tartaric and paratartaric acid and of their salts. 

"I soon recognized that . . . tartaric acid and all its combina- 


tions exhibit asymmetric forms. Individually, each of these forms 
of tartaric acid gave a mirror image which was not superposable 
upon the substance itself. On the contrary, I could not find any- 
thing of the sort in paratartaric acid or its salts. 

"Suddenly, I was seized by a great emotion. I had always kept 
in mind the profound surprise caused in me by Mitscherlich's 
note on the tartrate and paratartrate of sodium and ammonium. 
Despite the extreme thoroughness of their study, I thought, Mit- 
scherlich, as well as M. de la Provostaye, will have failed to notice 
that the tartrate is asymmetric, as it must be; nor will they have 
seen that the paratartrate is not asymmetric, which is also very 
likely. Immediately,, and with a feverish ardor, I prepared the 
double tartrate of sodium and ammonium, as well as the cor- 
responding paratartrate, and proceeded to compare their crystal- 
line forms, with the preconceived notion that I would find asym- 
metry in the tartrate and not in the paratartrate. Thus, I thought, 
everything will become clear; the mystery of Mitscherlich's note 
will be solved, the asymmetry in the form of the tartrate crystal 
will correspond to its optical asymmetry, and the absence of 
asymmetry in the form of the paratartrate will correspond to 
the inability of this salt to deviate the plane of polarized light. 
. . . And indeed, I saw that the crystals of the tartrates of sodium 
and ammonium exhibited the small facets revealing asymmetry; 
but when I turned to examine the shape of the crystals of para- 
tartrate, for an instant my heart stopped beating: all the crystals 
exhibited the facets of asymmetry! 

"The fortunate idea came to me to orient my crystals with 
reference to a plane perpendicular to the observer, and then I 
noticed that the confused mass of crystals of paratartrate could 
be divided into two groups according to the orientation of their 
facets of asymmetry. In one group, the facet of asymmetry nearer 
my body was inclined to my right with reference to the plane of 
orientation which I just mentioned, whereas the facet of asym- 
metry was inclined to my left in the other. The paratartrate ap- 
peared as a mixture of two kinds of crystals, some asymmetric 
to the right, some asymmetric to the left. 

SP b 

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"A new and obvious idea soon occurred to me. These crystals 
asymmetric to the right, which I could separate manually from 
the others, exhibited an absolute identity of shape with those of 
the classical right tartrate. Pursuing my preconceived idea, in the 
logic of its deductions, I separated these right crystals from 
the crystallized paratartrate; I made the lead salt and isolated the 
acid; this acid appeared absolutely identical with the tartaric 
acid of grape, identical also in its action on polarized light. My 
happiness was even greater the day when, separating now from 
the paratartrate the crystals with asymmetry at their left, and 
making their acid, I obtained a tartaric acid absolutely similai 
to the tartaric acid of grape, but with an opposite asymmetry, 
and also with an opposite action on light. Its shape was iden- 
tical to that of the mirror image of the right tartaric acid and, 
other things being equal, it rotated light to the left as much in 
absolute amount as the other acid did it to the right 

"Finally, when I mixed solutions containing equal weights of 
these two acids, the mixture gave rise to a crystalline mass of 
paratartaric acid identical with the known paratartaric acid." 

The enthusiastic Balard quickly broadcast into scientific circles 
the news of these unexpected findings, and Pasteur was thus 
brought into contact with Biot, who, throughout his long and 
laborious career, had contributed so much knowledge to the 
problems of crystallography and optical activity. It was Biot who 
had presented to the Academy, three years before, the note by 
Mitscherlich which had so much perplexed Pasteur. It was he 
again who was asked to present the new discovery. But before 
doing so, the skeptical veteran submitted the young man's almost 
suspiciously plausible results to a stringent verification. 

Pasteur has left the following account of his first dealings with 

"He (M. Biot) sent for me to repeat before his eyes the sev- 
eral experiments and gave me a sample of racemic acid which 
he had himself previously examined and found to be quite in- 
active toward polarized light. I prepared from it, in his pres- 


ence, the sodium ammonium double salt, for which he also de- 
sired himself to provide the soda and ammonia. The liquid was 
set aside for slow evaporation in one of the rooms of his own 
laboratory, and when thirty to forty grams of crystals had sepa- 
rated, he again summoned me to the College de France, so that 
I might collect the dextro and levorotatory crystals before his 
eyes, and separate them according to their crystallographic char- 
acter asking me to repeat the statement that the crystals which 
I should place on his right hand would cause deviation to the 
right, and the others to the left. This done, he said that he him- 
self would do the rest He prepared the carefully weighed solu- 
tions, and at the moment when he was about to examine them in 
the polarimeter, he again called me into his laboratory. He first 
put into the apparatus the more interesting solution, the one 
which was to cause rotation to the left. Without making a read- 
ing, but already at the first sight of the color tints presented by 
the two halves of the field in the Soleil polarimeter, he recognized 
that there was a strong levorotation. Then the illustrious old man, 
who was visibly moved, seized me by the hand, and said, *My 
dear son, I have loved science so deeply that this stirs my heart/ " 

Thus, the first phase of Pasteur's experimental investigations 
had established the existence of three tartaric acids, differen- 
tiated by the orientation of facets on their crystals and by the 
corresponding optical activity, but otherwise identical in chemical 
properties. Two lectures which Pasteur presented in 1860 before 
the Societe Chimique de Paris give us his interpretation of the 
new phenomena and particularly the mental picture which he 
had formed of the molecular configuration responsible for optical 
activity. The intellectual achievement involved in the formulation 
of this picture appears the more striking when it is remembered 
that the science of structural organic chemistry was not yet born 
and that the concept of the asymmetric carbon atom was still 
several decades away. 

"In isomeric bodies, the elements and the proportions in which 
they are combined are the same, only the arrangement of the 
atoms is different The great interest attaching to isomerism lies 


in the principle that bodies can be and realy are distinct, through 
possessing different arrangements of their atoms within their 
molecules. . . . We know, on the one hand, that the molecular 
arrangements of the two tartaiic acids are asymmetric, and, on 
the other hand, that these arrangements are absolutely identical, 
excepting that they exhibit asymmetry in opposite directions. 
Are the atoms of the dextro acid grouped in the form of a right- 
handed spiral, or are they placed at the apex of an irregular 
tetrahedron, or are they disposed according to this or that asym- 
metric arrangement? We do not know. But there can be no doubt 
that we are dealing with an asymmetric arrangement of the atoms, 
giving a non-superposable image. It is equally certain that the 
atoms of the levo-acid are disposed in an exactly opposite man- 
ner. Finally, we know that racemic acid is formed by the union 
of these two groups of oppositely arranged asymmetric atoms. 

"Quartz . . you will say at once . . . possesses the two char- 
acteristics of asymmetry hemihedry in form, observed by Haiiy, 
and the optical activity discovered by Arago! Nevertheless, molec- 
ular asymmetry is entirely absent in quartz. To understand this, 
let us take a further step in the knowledge of the phenomena 
with which we are dealing. 

"Permit me to illustrate roughly, although with essential ac- 
curacy, the structure of quartz and of the natural organic prod- 
ucts. Imagine a spiral stairway whose steps are cubes, or any other 
objects with superposable images. Destroy the structure of the 
stairway and the asymmetry will have vanished. The asymmetry 
of the stairway was simply the result of the mode of arrangement 
of the component steps. Such is quartz. The crystal of quartz is 
the stair complete. It is hemihedral. It acts on polarized light by 
virtue of this. But let the crystal be dissolved, fused, or have its 
physical structure destroyed in any way whatever; its asymmetry 
is suppressed and with it all action on polarized light, as it would 
be, for example, with a solution of alum, a liquid formed of mole- 
cules of cubic structure distributed without order. 

"Imagine, on the other hand, the same spiral stairway to be 
constructed with irregular tetrahedra for steps. Destroy the stair- 


way, and the asymmetry will still exist, since we are dealing with 
a collection of tetrahedra. They may occupy any positions what- 
soever, yet each of them will, nevertheless, have an asymmetry 
of its own. Such are the organic substances in which all the 
molecules have an asymmetry of their own, revealing itself in 
the crystalline form. When the crystal is destroyed by solution, 
there results a liquid of molecules, without arrangement, it is 
true, but each having an asymmetry in the same sense, if not of 
the same intensity in all directions." 

Pasteur then summarized his views in the following conclu- 
sions : 

'When the atoms of organic compounds are asymmetrically 
arranged, the molecular asymmetry is betrayed by crystalline 
form exhibiting non-superposable hemihedrism. The presence of 
molecular asymmetry reveals itself by optical activity. When this 
non-superposable molecular asymmetry appears in two opposed 
forms, as in the case of 'dextro* and levo* tartaric acids and all 
their derivatives, then the chemical properties of the identical 
but optically opposite substances are exactly the same, from 
which it follows that this type of contrast and analogy does not 
interfere with the ordinary play of the chemical affinities/' 

Although the investigation of tartrates had been suggested and 
guided by the preconceived idea that molecular asymmetry must 
find expression both in optical activity and in asymmetry of 
crystalline shape, Pasteur himself was soon to find out that the 
relationship does not always hold true. He had been fortunate in 
beginning his investigation with the tartrates for, among sub- 
stances endowed with optical activity, they present in the simplest 
form the relation between chemical structure, crystalline morphol- 
ogy and deviation of polarized light. One might be tempted, 
therefore, to attribute his success to luck. However, so often was 
Pasteur helped by apparent "luck" in the subsequent course of his 
scientific career that the reason for his success must be found 
elsewhere. Throughout his life, he displayed an uncanny gift in 
selecting the type of experimental material best adapted to the 
solution of the problem under investigation. This gift, which is 


common to all great experimenters, certainly consists in part of an 
intuitive wisdom based upon a large background of knowledge. 
Good fortune is offered to many, but few are they who can rec- 
ognize it when it is offered in a not too obvious manner. 

Pasteur could have been thinking of many vital experiences of 
his own when he reiterated, time and time again, "In the field of 
experimentation,, chance favors only the prepared mind." 

So it was that, by the age of twenty-seven, Pasteur had already 
given evidence of the qualities which were to make him a great 
investigator. He had had the independence and the audacity to 
question the validity of statements made by a scientist of ac- 
knowledged authority. He had formulated a bold working hy- 
pothesis in terms amenable to study by available experimental 
methods. With industry and thoroughness, he had prepared him- 
self to use these methods, not for the sake of their mastery, but 
in order to obtain an answer to the questions which he had in 
mind. The dominance of problems over technical procedures is 
one of the most striking aspects of his experimental genius. Once 
he had recognized and formulated a problem, he was able to 
bring to bear on its solution any available technique, be it physi- 
cal, chemical or biological; he was always wining to devote him- 
self to the mastery of the experimental methods best suited to 
give an answer to his questions. 

Neither the pressure of his teaching duties, nor his marriage in 
1849, could deter Pasteur from exploiting the scientific vein which 
he had uncovered. In later years, he referred to youth as "the 
time when the spirit of invention flourishes," In his case, the 
flowering was a burst of experiments and of ideas, a few of them 
faulty, some visionary, but all equally interesting. Never did the 
spirit of invention germinate in the form of more unexpected and 
at times fantastic flowers. So much happened over such a short 
period of time, that a chronological recital would give only an im- 
pression of confusion and would indeed be untrue to the intel- 
lectual processes which powered Pasteur's activities. As we know, 


the initial discoveries on tartaric acids opened a number of inde- 
pendent channels of investigation, and Pasteur attempted to split 
his energy so as to follow all of them simultaneously. We shall 
be less ambitious, and at the cost of losing much of the excite- 
ment of the chase, follow, one after the other, a few of the trails 
which he cleared between 1850 and 1857. 

As mentioned earlier., Pasteur had made a fortunate choice in 
using the tartaric acid series to master the art of crystallography 
and to investigate the relation of crystalline structure to optical 
activity. Chance had also favored him in making paratartaric 
acid become available shortly before he began his scientific 
career. For unknown reasons, however, this peculiar acid had 
now become extremely scarce and failed to appear again, even in 
the Thann factory where it was formerly so abundant. Moreover, 
no chemical technique was known to produce it in the laboratory 
and for this reason, the Societe de Pharmacie of Paris instituted 
a prize of 1500 francs for the first chemical synthesis of the 
mysterious substance. Pasteur was naturally much perplexed by 
this situation and wondered, in particular, what could be the 
origin of the acid to which he owed his first scientific laurels. 

In 1852, Mitscherlich having asked for an opportunity to meet 
tie young Pasteur, Biot arranged at his home a first meeting 
which was followed by a dinner at Baron Thenard's. Pasteur's 
account of this event in a letter to his father glows with his naive 
pride at being in such distinguished company. "You will like to 
see the names of the guests: Messrs. Mitscherlich, Rose, Dumas, 
Chevreul, Regnault, Pelouze, P^ligot, Prevost and Bussy. As you 
will notice, I was the only outsider; they are all members of the 
Academy." Of especial interest for him was his discovering at that 
dinner that a Saxony manufacturer was again producing para- 
tartaric acid. Mitscherlich believed that the tartars from the wine 
fermentation vats employed by this manufacturer came from 
Trieste; in 1820, the Thann manufacturer Kestner had received 
his crude tartars from Naples, Sicily or Oporto. Whence came 
paratartaric acid? and why had it disappeared? The problem, 







chemical In nature, demanded the techniques of the explorer and 
of the detective for its solution. Without hesitation and despite 
financial difficulties > Pasteur started on a hunt over Central Eu- 
rope to trace the origins of the mysterious acid. 

In. detailed letters to his wife, the traveling neophyte marveled 
that the world outside of France should be so civilized and pol- 
ished. He visited professors and manufacturers in Leipzig, Frei- 
burg, Vienna, Prague, proud to see his name already well known 
to fellow scientists. He spent his spare time studying in hotel 
rooms the game collected in his scientific hunt and finally, in 
Prague, obtained convincing evidence that paratartaric acid was 
always present in the mother liquor remaining after purification 
of the crude tartars, but was being progressively eliminated from 
the true tartaric acid in the course of purification. Apparently it 
was only an accident of manufacture which had allowed it to ac- 
cumulate in relative abundance in the Thann factory a few dec- 
ades earlier. Homesick, tired and divested of funds, Pasteur re- 
turned to Strasbourg, satisfied with having achieved his ends. An 
account of his journey in the newspaper La Verite contained a 
sentence which amused everyone, Pasteur included. "Never was 
treasure sought, never adored beauty pursued over hill and dale 
with greater ardor." 

It is somewhat difficult today to justify so much enthusiasm. 
One wonders whether Pasteur did not judge of the importance of 
paratartaric acid in the realm of chemistry from what it had 
meant for his own life, a common and forgivable sin. If this trip 
has not remained one of the great journeys of science, as its hero 
considered it to be, at least it illustrates the determination and 
energy with which Pasteur approached any problem. It gave him, 
moreover, the opportunity of investigating the claims of German 
workers who thought that they had succeeded in producing para- 
tartaric acid by chemical synthesis. He had no difficulty in dis- 
proving these claims and returned to Strasbourg determined to be 
the first to perform this chemical feat In fact, he succeeded, in 
June 1853 synthesizing paratartaric acid by maintaining tartrate 
of cinchonine at a high temperature for several hours. That he was 


intoxicated by what he considered a world-shaking discovery is 
revealed in a letter to his father. "My dear father, I have just sent 
the following telegram: 'Monsieur Biot, College de France, Paris. 
I transform tartaric acid into racemic acid; please inform MM. 
Dumas and Senarmont* Here is, at last, that racemic acid (which 
I traveled to Vienna to find), artificially obtained from tartaric 
acid. I long believed this transformation to be impossible. This 
discovery will have incalculable consequences." 

The consequences were indeed by no means unimportant, al- 
though they were hardly the ones that he may have had in mind. 
The same operation which had yielded synthetic paratartaric acid 
also gave a fourth form of tartaric acid mesotartaric acid 
which, although optically inactive, was quite distinct from para- 
tartaric acid in not being susceptible of resolution into left and 
right tartaric acids. 

The work on tartrates had made it of obvious interest to estab- 
lish whether the relation between optical activity and crystalline 
structure was a property peculiar to the tartaric acid series, or 
whether other organic substances exhibiting optical activity 
would also present evidence of morphological asymmetry in the 
crystalline state. Unfortunately, few organic substances gave 
crystals adequate for study by the methods then available. Among 
those which formed beautiful crystals were asparagine and its 
derivatives: aspartic acid and malic acid. Pasteur therefore made 
haste to study them. 

As asparagine was then a rare substance, he prepared large 
amounts of it from vetch which he grew in the gardens and 
cellars of the University at Strasbourg and recognized with 
satisfaction that asparagine crystals exhibited facets and were 
endowed with optical activity. Aspartic acid and malic acid, de- 
rived from asparagine, also deviated the plane of polarized light, 
but in these cases the relation of optical activity to crystalline 
structure was either lacking or less clear than in the case of the 
tartrates. The different active and inactive aspartates, although 
very similar chemically, were entirely different from the point of 


view of crystallography, even presenting apparently incompatible 
shapes. The active and inactive malates, also very similar chemi- 
cally, failed to give evidence of correlation between the inclina- 
tion of the facets on the crystals and the direction of the rotation 
of light. Thus, the beautiful relation shown by the tartrates be- 
tween optical activity and crystalline structure was not always 
obvious in the case of other related substances. Nevertheless, so 
convinced was Pasteur of the significance of his early findings 
that he was not too much concerned with the apparent inconsist- 
encies which he was now encountering. Instead, he assumed with 
a tranquil assurance that crystalline shape was of only secondary 
importance, and while not abandoning his belief that there ex- 
isted some subtle correlation between crystal structure and opti- 
cal activity, he concluded that the latter property was the more 
constant and fundamental expression of asymmetry within the 
molecule itself. Furthermore, he reasoned that if there is a com- 
mon atomic grouping between the right-handed tartaric acid of 
the grape and natural malic acid, the atomic grouping of the left- 
handed tartaric acid must also have its counterpart in a malic 
acid still unknown which, when discovered, would be a levo 
compound. The growth of the science of organic chemistry was 
soon to prove him right. Thus even before stereochemistry had de- 
veloped its doctrines and its body of factual knowledge, Pasteur 
was bold enough to anticipate its unborn concepts and forecast 
the existence of "levo" malic acid. 

Pasteur had first separated the oppositely active components 
of the inactive paratartrate by picking them manually, taking ad- 
vantage of the orientation of their facets. This laborious method 
was slightly modified later by his student Gernez, who achieved 
the separation by introducing into the supersaturated solution a 
crystal of just one of the active components, a procedure some- 
times resulting in the selective crystallization of the added com- 

Pasteur soon arrived at a second fundamentally different 
method, which he introduced with the following reasoning; 


"The properties of the two tartaric acids and their derivatives 
appear identical as long as they are brought into contact with 
. . . potash, soda, ammonia, lime, baryta, aniline, alcohol, the 
ethers, in short with substances devoid of asymmetry. . . . 

"On the contrary, if they are subjected to the action of ... 
asparagiae, quinine, strychnine, bracine, albumin, sugar, et cetera, 
asymmetric like themselves, then the two tartrates exhibit differ- 
ent behavior. The solubility of their salts is different. If combina- 
tion takes place, the products differ from each other in crystalline 
form, in specific gravity, in the amount of water of crystallization, 
in stability on heating, in fact just in the same way as the most 
distantly related isomers can differ from each other. 

The knowledge that salts of dextro and levo tartaric acid can 
acquire such different properties only through the optical activity 
of the base with which they combine, justified the hope that this 
difference . . . would afford a means of splitting racemic acid 
into its components. Many are the abortive attempts which I have 
made in this direction, but I have at length achieved success with 
the help of two new asymmetric bases, quinidine and cinchoni- 
dine, which I can very easily obtain from quinine and cinchonine 
respectively. . . . 

"I prepare the cinchonidine racemate by first neutralizing the 
base and then adding as much acid again. The first crystals to 
separate are perfectly pure cinchonidine levo tartrate. The whole 
of the dextro tartrate remains in the mother liquor, as it is more 
soluble; gradually this also crystallizes out, but in forms which 
are totally distinct from those of the levo tartrate." 

It was in 1857, at the end of the period we are now considering, 
that Pasteur discovered a third method for the fractionation of 
optically inactive compounds into their "right* and "left* com- 
ponents. This method, which is in some respects the most remark- 
able of the three, was the result of one of those chance occur- 
rences which are observed and seized upon only by the prepared 

It had long been known that impure solutions of calcium tar- 
trate occasionally became turbid and were fermented by a mold 


during warm weather, and Pasteur noticed one day that a tartrate 
solution of his had become thus affected. Under the circum- 
stances, most chemists would have poured the liquid down the 
sink, considering the experiment as entirely spoiled. But an inter- 
esting problem at once suggested itself to his active mind; how 
would the two forms composing the paratartaric acid be affected 
under similar conditions? To his intense interest, he found that 
whereas the dextro form of tartaric acid was readily destroyed 
by the fermentation process, the levo form remained unaltered. 
Pasteur's own account of the changes which occurred in a solu- 
tion of paratartrate infected with fermenting fluid reveals his 
power to proceed from trivial observations to broad theoretical 
concepts. As we shall see, the selective destruction of dextro tar- 
taric acid was the first link in the chain of arguments which led 
him into the study of fermentations and of contagious diseases. 

"The solution of paratartrate, at first optically inactive, soon 
becomes perceptibly levorotatory, and the rotation gradually in- 
creases and attains a maximum. The fermentation then stops. 
There is now no trace of the dextro tartaric acid left in the liquid, 
which on being evaporated and treated with an equal volume of 
alcohol yields a fine crop of crystals of ammonium levo tartrate. 

Two different aspects of this phenomenon require emphasis, 
As in every true fermentation, there is a substance undergoing 
chemical alteration, and corresponding with this there is the de- 
velopment of a moldlike organism. On the other hand, and it is 
precisely to this point that I should like to draw your attention, 
the levo salt is left untouched by the mold which causes the de- 
struction of the dextro salt, and this despite the identity of the 
physical and chemical properties of the two salts that prevails as 
long as they are not submitted to asymmetric influences. 

"Here then we see molecular asymmetry, a property peculiar 
to organic matter, influencing a physiological process, and influ- 
encing it, moreover, by modifying the chemical affinities. . . . 

"Thus, the concept of the influence of molecular asymmetry 
of natural organic products is introduced into physiological 
studies, through this important criterion (optical activity), which 


forms perhaps the only sharply defined boundary which can "be 
drawn at the present time between the chemistry of dead and 
that of living matter/ 7 

Even before 1857 Pasteur had become convinced that one of 
the fundamental characteristics of living matter was its asym- 
metric nature. This view became one of the cardinal tenets of his 
biochemical thinking, one to which he returned throughout his 
life; thus in 1886, thirty years after he had abandoned experi- 
mentation on molecular asymmetry, he discussed a paper on the 
two asparagines of opposite optical activity presented by one of 
his colleagues in the Academy of Sciences, and he called atten- 
tion to the fact that one of the asparagines is sweet to the taste 
while its optical antipode is insipid, suggesting that this difference 
might be due to a different action of the two asymmetric antipodes 
on the asymmetric constituents of the gustatory nerve. 

Biot, it will be recalled, had discovered that certain organic 
materials sugar, albumin, turpentine, and the like rotate the 
plane of polarized light. On the basis of his own experience, Pas- 
teur was soon in a position to remark that, in contrast to the be- 
havior of the majority of these naturally occurring substances, 
the artificial products of the laboratory are without optical activ- 
ity; and he became possessed by the idea that molecular asym- 
metry can be produced only through a vital agency. His precon- 
ceived views appeared shattered when in 1850 Dessaignes, a 
French chemist from Vendome, announced that he had obtained 
aspartic acid identical with the natural product by heating the 
ammonium salts of fumaric and maleic acids, two substances 
known to be optically inactive. Dessaignes thus claimed to have 
accomplished what Pasteur firmly believed to be impossible, 
namely the preparation by chemical means of an optically active 
molecule (aspartic acid) from inactive ones (fumaric or maleic 
acids). Pasteur hastened at once from Strasbourg to Vendome 
and obtained from Dessaignes a specimen of his artificial aspartic 
acid; he soon had the satisfaction of showing that the latter sub- 
stance was optically inactive and therefore not really identical 


with the natural aspartic acid. Furthermore he converted this in- 
active aspartic acid into maHc acid, and in accordance with his 
anticipations, found that this malic acid differed from the natural 
one in being also inactive toward polarized light 

Pasteur's triumph was apparently complete, but it was now 
necessary to account for the existence of these new forms of 
synthetic aspartic and malic acids which were different from the 
natural products. The work involved in their study led to a 
comedy of errors in which Pasteur made a spectacular discovery 
on the basis of false theoretical concepts. Because of his precon- 
ceived idea that optically active substances could not be synthe- 
sized by chemical methods, he did not even consider that the 
synthetic malic acid which he had produced might be a mixture 
in equal amounts of the right and left maHc acids. How could he 
have imagined the simultaneous synthesis of two optically active 
compounds when he considered the synthesis of one as unreal- 
izable? In order to account for the production of optically inactive 
malic acid by synthesis, he therefore postulated the existence of 
a new class of substances in which the asymmetry was abolished 
by some internal rearrangement of the atoms, instead of by the 
mixture of two molecules of opposite character as in the case of 
paratartaric acid. This interpretation was proved wrong when it 
was shown that, contrary to his prejudiced notion, the inactive 
malic acid which he had synthesized was nothing but a mixture 
of optically active antipodes. 

Nevertheless, Pasteur's hypothesis of a new type of molecule 
was soon confirmed under unexpected circumstances. While 
working on the synthesis of paratartaric acid from tartaric acid, 
he obtained in addition to the former a new form of optically 
inactive tartaric acid mesotartaric acid that could not be re- 
solved into left and right components; this new compound cor- 
responded to the molecular structure which he had postulated. 
Thus, in the very act of putting the wrong interpretation on the 
nature of inactive malic acid, he had made a most important addi- 
tion to the theory of molecular structure. He had postulated and 
demonstrated the existence of a new type of optically inactive 


molecules, namely one in which the compound is neither dextro 
nor levorotatory, nor formed by the union of these. It is now well 
known that this type of molecule does not exist for every asym- 
metric compound, as was erroneously assumed by Pasteur, but 
only for those which, like tartaric acid and the tetra- and hexa- 
hydric alcohols and the hydroxy dibasic acids, can have their 
molecules divided into two symmetrical halves, the optical effect 
of the one half neutralizing the optical effect of the other within 
the molecule. 

In 1860, Perkin and Duppa prepared from succinic acid by syn- 
thetic reaction a substance which Pasteur himself identified as 
paratartaric acid, and they achieved thereby the synthesis not 
only of one, but actually of two asymmetric molecules. Had Pas- 
teur slightly modified the terms of his dogma of the impossibility 
of producing asymmetric molecules by synthesis, it might still 
stand unchallenged. For even today, the synthesis from sym- 
metric materials of a single asymmetric molecule, without at the 
same time building up an equal number of asymmetric molecules 
of configuration opposite to the first, can be accomplished only 
by introducing an asymmetric element into the reaction. The re- 
lationship between optical activity and life still appears to be as 
close as suspected by Pasteur. La a certain measure, optically 
active compounds may be compared with living organisms, for 
just as they can convert inanimate material into organic, similarly 
it is possible to synthesize from optically active compounds other 
optically active substances which bear a certain qualitative rela- 
tionship to the original active compound. 

Pasteur affirmed to the last that, in final analysis, asymmetric 
bodies are always the products of living processes. In order to ac- 
count for the selective accumulation of either the right or the left 
form of a given substance during the course of living processes, 
one might conceive that the two forms are produced simulta- 
neously but one of them is utilized or destroyed as fast as pro- 
duced. Pasteur adopted another view which, in fact, is not exclu- 
sive of the first. He boldly connected the asymmetry of natural 


products with the presence of asymmetry In the forces acting 
upon them at the time of their formation. Although the earth is 
round, he pointed out, it would be symmetrical and superposable 
on itself only if motionless. As soon as it turns on its axis, its 
image in a mirror no longer resembles it, as the image turns in a 
different direction. If there is an electric current flowing along 
the equator and presiding over the distribution of magnetism, 
this current also turns in opposite directions in the earth and in 
its image. In short, the earth is an asymmetrical whole from the 
point of view of the forces which make it live and function, and 
of the things which it produces. It is for this reason, Pasteur felt, 
that the substances produced by living creatures are asymmetrical 
and endowed with optical activity. If some asymmetric forces 
were in operation at the time of the genesis of a plant, it might 
initiate an asymmetric process which would then render asym- 
metric all subsequent biological operations. Protoplasm, in other 
words, would thus be made asymmetrical when first produced. 

These imaginings fired Pasteur's mind and he spoke of them 
with uncontrolled enthusiasm on several occasions. 

"The universe is an asymmetrical whole. I am inclined to think 
that life, as manifested to us, is a function of the asymmetry of 
the universe and of the consequences it produces. The universe is 
asymmetrical; for, if the whole of the bodies which compose the 
solar system moving with their individual movements were placed 
before a glass, the image in the glass could not be superposed 
upon the reality. Even the movement of solar light is asym- 
metrical. A luminous ray never strikes in a straight line upon the 
leaf where plant life creates organic matter. Terrestrial magnet- 
ism, the opposition which exists between the north and south 
poles in a magnet and between positive and negative electricity, 
are but resultants of asymmetrical actions and movements. . . . 

"Life is dominated by asymmetrical actions. I can even imagine 
that all living species are primordially, in their structure, in their 
external forms, functions of cosmic asymmetry." 

Nor did Pasteur simply propound these questions. Instead, he 
was bold enough to attempt experimentation in this highly specu- 


lative domain, hoping to duplicate in the laboratory the asym- 
metrical effects which he assumed to preside over the synthesis 
o organic materials in nature. For a while he considered the pos- 
sibility that the barrier which separates the synthetic products 
of the laboratory from those formed under the influence of life 
might not be an impassable one. If it be true that nature elabo- 
rates the living substances by means of asymmetrical forces, why 
should not the chemist attempt to imitate nature? Why should 
he not bring asymmetrical forces to bear upon the production of 
chemical phenomena instead of limiting himself to methods 
founded upon the exclusive use of symmetrical forces? While in 
Strasbourg, Pasteur had powerful magnets constructed with a 
view to introducing asymmetrical influences during the forma- 
tion of crystals. At Lille, in 1854, he had a clockwork arrangement 
made with which he intended, by means of a heliostat and re- 
flector, to reverse the natural movement of the solar rays striking 
a plant, from its birth to its death, so as to see whether, in such 
an artificial world in which the sun rose in the west and set in 
the east the optically active substances would not appear in 
forms opposite to those occurring in the normal order of nature. 
His faithful advisers warned him that he risked sacrificing much 
energy, time and resources to no avail on these fantastic experi- 
ments. Worldly-wise enough to realize that he had a better chance 
of success in working toward more limited objectives, Pasteur 
eventually abandoned his ambitious projects without having 
achieved any results. But he never forgot his romantic ideas, his 
alchemist dream of unraveling the chemical riddle of life. Time 
and time again, he referred to them in conversations, lectures and 
unpublished notes. During and after the war of 1870, while he 
was forced to remain away from his laboratory, he returned once 
more to the thoughts of his early years, and discussed them in a 
letter to his assistant Raulin. 

"I have begun here some experiments on crystallization which 
will open great prospects, should they lead to positive results. As 
you know, I believe that there exists in the universe an asym- 
metrical influence which presides constantly and naturally over 


the molecular organization of principles immediately essential to 
life. In consequence, the species of the three kingdoms bear a 
definite relation to the movements of the universe by their struc- 
ture, by their form, by the disposition of their tissues. For many 
of these species, if not for all, the sun is the primum movens of 
nutrition; but 1 believe in another influence which would affect 
the whole organization, for it would be the cause of the molecular 
asymmetry proper to the chemical components of life. I would 
like to grasp by experiment a few indications of the nature of this 
great cosmic asymmetrical influence. It may be electricity, mag- 
netism. . . . And, as one should always proceed from the simple 
to the complex, I am now trying to crystallize double race- 
mate of soda and ammonia under the influence of a spiral sole- 

Intoxicated by his imagination, Pasteur thus attempted to alter 
the course of chemical synthesis, and even to create or modify 
life by means of asymmetrical forces. What would a world be, he 
wondered, in which sugar, cellulose, albumins, and other organic 
materials would consist of molecules oriented differently from the 
ones which we know? Although he never gave up these dreams, 
he became increasingly aware in later years of the difficulties pre- 
sented by their experimental realization, especially after his 
studies on spontaneous generation had convinced him of the over- 
whelming directional effect of the "germ" on the development of 
living things. It seems that only one of his collaborators and dis- 
ciples, Duclaux, has spoken with warmth and sympathy of these 
projects, to the extent of himself elaborating on a statement made 
by the master in 1874. "In order to introduce into a cell proximate 
principles different from those which exist there, it would be 
necessary to act upon it at the time of its greatest plasticity, that 
is, to take the germ cell and try to modify it But this cell has re- 
ceived from its parents a heredity in the form of one or several 
active substances, the presence of which is sufficient to render it 
rebellious to certain actions and ... to impart to its evolution 
a definite direction. This cell contains in the beginning not only its 
being but also its becoming, and it constitutes therefore an initial 


force that . . . gives Its own direction to new forces which 
appear every day in the little world it governs. . . . 

"Ah, if spontaneous generation were possible! If one . . . could 
cause a living cell to evolve from inactive mineral matter! How 
much easier it would be to give it a direction, to make these 
asymmetries . . . enter into its substance and thence into its vital 
manifestations. I am adding something to what Pasteur has writ- 
ten on these captivating questions, but I do not believe that I have 
gone beyond what was in his thought in my effort to show how 
... he arrived at two of the problems which it was fated that he 
should solve: the question of fermentations and that of sponta- 
neous generations." 

Pasteur carried with him into the grave the dream of his scien- 
tific youth the fantastic vision of developing techniques for 
the creation or the modification of life by introducing asymmetri- 
cal forces into chemical reactions. Duclaux was probably right in 
regarding the subsequent studies on spontaneous generation and 
fermentations as consequences of the early visions of the master. 
Indeed, it is a striking fact, perhaps worthy of the attention of 
psychoanalysts, that Pasteur devoted much of his later life to 
demonstrating that nature operates as if it were impossible to 
achieve what he Pasteur had failed to do. For he proved that 
all claims of the creation of life out of lif eless material were based 
on faulty observation or unskilled experiments, that spontaneous 
generation has never been observed; that, as far as one knows, 
life always conies from a "germ," from life. He demonstrated also 
that this "germ" imparts upon the new Me which it creates a di- 
rectional force so intense that each living being, however simple, 
possesses a specificity of property and functions peculiar to it. 
Each microbe, Pasteur would show, is the specific agent of a par- 
ticular fermentation, of a particular disease. Just as he had failed 
in his attempts to create or modify life, so he proved that others, 
who had claimed to be successful where he had failed, had been 
merely the victims of illusion. 

It was one of Pasteur's characteristics that, while often dream- 
ing romantic concepts, he possessed to an extreme degree the 


ability of observing small concrete facts which soon brought his 
activity back to the level of the possible. In the midst of his con- 
cern with the philosophical consequences of the optical activity 
of organic matter, he once observed that optically active amyl 
alcohol was a constant product of alcoholic fermentation. This 
was enough to suggest that amyi alcohol was another of the prod- 
ucts of life to be added to the list of optically active organic mate- 
rials first studied by the venerated Biot Alcoholic fermentation, 
then, was a manifestation of life. It was this conviction that 
launched Pasteur on a new sea of experiments, on the tempestuous 
voyage from which he was to bring back the germ theory of fer- 
mentation and of disease. 


The Domestication of Microbial Life 

There is a devil in every berry of the grape. 


SHOKIX.Y after Pasteur's arrival in Lille, the father of one of Ms 
students Bigo by name came to consult him concerning diffi- 
culties that he was experiencing with the alcoholic fermentation 
of beet sugar in his distillery. Pasteur agreed to investigate the 
matter, spent some time almost daily at M. Bigo's factory and, as 
shown by his laboratory notebooks, began to study alcoholic fer- 
mentation in November of the same year. This experience awoke 
in him an interest in the broader aspects of the fermentation prob- 
lem and, by the spring of 1857, he was investigating the produc- 
tion not only of alcohol, but also of lactic, butyric and tartaric 
acids by fermentation reactions. 

The word "fermentation" was then loosely applied to the spon- 
taneous changes which often occur in organic solutions and which 
result in the production of spirituous or acidic substances. The 
production of alcohol during the making of wine, beer, or cider 
was called "alcoholic fermentation"; the conversion of wine or 
cider into vinegar, the ^acetic acid fermentation"; the souring of 
milk, during which milk sugar is converted into lactic acid, the 
'lactic acid fermentation." It was also well known that many 
natural materials, such as meat, eggs, bouillons, could sponta- 
neously undergo other types of changes which were designated 
by the word "putrefaction." Putrefaction was generally assumed 
to be closely related to fermentation, but to differ from it in the 


products formed, as evident from the il-smeHlng emanations 
which accompany the former process. 

The man of science as weU as the layman of 1850 regarded fer- 
mentations and putrefactions as caused by chemical agents the 
"ferments'* complex and obscure, true enough, but no more ob- 
scure than those involved in the chemical reactions classified by 
the Swedish chemist Berzelius under the name of "catalytic proc- 
esses." According to Berzelius, the catalyst, or the ferment, acted 
by its mere presence to start the reaction without becoming a part 
of it, much as lightning or a hot cannon ball can start a fire, with- 
out supplying the fuel which keeps it going. Berzelius regarded 
catalysts (or ferments) as "bodies that were capable, by their 
mere presence ... of arousing affinities ordinarily quiescent at 
the temperature of the experiment, so that the elements of a com- 
pound body arrange themselves in some different way, by which 
a greater degree of electrochemical neutralization is attained." 
Thus there were alcoholic, lactic acid, butyric acid, acetic acid, 
putrefaction ferments all catalysts capable in some mysterious 
manner of bringing about the formation of the substance for 
which they were named. The ferment responsible for the pro- 
duction of alcohol was also known under the name of yeast, as 
was the leaven active in the rising of the dough during the mak- 
ing of bread. 

The processes of fermentation constitute some of the first suc- 
cesses of technology. Even before the dawn of history, man 
learned to use yeast to transform the difficult-to-digest starch paste 
into light and savory bread, an achievement which contributed 
much to the pleasure of life and perhaps to the development of 
our civilization. With yeast, also, he learned to produce, from 
sweet and spiritless solutions, the volatile and stimulating liquids 
which have received in all languages names suggesting spirits and 
the power of life because of their multiple and strange virtues. All 
ancient folklores have associated the activity of yeast with the 
phenomena of life; indeed, bread and wine became the symbol 
of Life Eternal in the Mediterranean religions. In addition to the 


magic of their results, the nature of the processes initiated by 
yeast caught the fancy of philosophers and chemists. The bub- 
bling that takes place spontaneously in the mass of vintage, or in 
the flour paste, appeared to them as the manifestation of some 
living spirit; fermentation became one of the favorite subjects for 
meditation and for experiments by the alchemists, and they de- 
rived from its study much of their language and ideology. The 
subtle changes in property that occur in the mass of fermenting 
material seemed to them the symbol of those mysterious forces 
which, instrumented by the philosopher's stone, could convert the 
baser metals into gold. 

With the advent of rational science, it became the ambition of 
natural philosophers of scientists to explain fermentation in 
more understandable terms. The chemists of the eighteenth and 
nineteenth centuries attempted to formulate alcoholic fermenta- 
tion by means of the chemical reactions and symbols which were 
proving so successful in describing other phenomena of nature. 
Whatever their philosophical or religious faith, the natural phi- 
losophers believed that nothing could better demonstrate the 
ability of the human mind to unravel the riddle of life than to 
succeed in explaining these mysterious fermentations. And in 
fact, they were essentially right if not in their surmises, then 
at least in their general view of the future course of science; for 
much of our understanding of the biochemical reactions of living 
processes has evolved from the study of yeast and of alcoholic fer- 
mentation. It is the enviable privilege of yeast and of the products 
of its activities that they have, directly or indirectly, fed the 
dreams and the follies of man, inspired poets, and challenged 
philosophers and scientists to meditation and creative think- 

Lavoisier, Gay-Lussac, Thenard, Dumas the high priests of 
Pasteur's scientific cult had studied the transformation of cane 
sugar into alcohol by the methods of quantitative chemistry. They 
had reached a formulation which appeared so exact as to give the 


illusion that the fundamental nature of the phenomenon had been 
finally discovered. 

According to Lavoisier, the sugar was split into two parts, one 
of which was oxidized at the expense of the other to form carbonic 
acid, while the second party losing its oxygen to the first, became 
the combustible substance, alcohol "so that if it were possible to 
recombine these two substances, alcohol and carbonic acid, sugar 
would result.** What could be clearer than this simple relation- 
ship? Lavoisier's formula was satisfactory except for the fact that 
there was in it no place for yeast. And yet, all chemists accepted 
as a fact that yeast always accompanied and probably initiated 
fermentation. Although it was the prime mover of the reaction, 
yeast did not appear to take part in it Berzelius explained away 
the puzzling question by the word "catalysis." 

The interpretation of alcoholic fermentation held by the nine- 
teenth-century chemists is, in certain respects, a forerunner of 
the modern physicochemical interpretation of living processes. 
One by one, all the activities of living things are being described 
in terms which, as they come to be better defined and their inter- 
relationships better understood, give an ever simpler and more 
satisfactory account of the forces and processes which together 
constitute life. But insofar as we know, the integration of all these 
physicochemical processes depends upon prior life. The twentieth- 
century biochemist does not know how to introduce life into his 
equilibrium reactions any better than the nineteenth-century 
chemist knew where to place yeast in the formula of alcoholic 
fermentation. However, so great were the triumphs of physico- 
chemical science during the "wonderful century" that many sci- 
entists had enough confidence, or perhaps merely enough intel- 
lectual conceit, to ignore the difficulty, and to refuse to recognize 
the existence of an unsolved mystery in fermentation and putre- 
faction. Pasteur was willing to reintroduce mystery in the problem 
by stating that yeast was a living being and fermentation an 
attribute of its life. He did not have to devise any radically new 
experimental approach to demonstrate this concept. In fact, the 
true relation of yeast to fermentation had been clearly stated by 


at least four experienced investigators before him, and probably 
recognized many more times by obscure and timid men who, 
awed by the authority of established science, had not dared to 
project their observations beyond the walls of their studies. 

In 1835, Cagniard de la Tour had observed that the yeast pro- 
duced during fermentation consisted of Mving cellular organisms 
which multiplied by budding, and he suggested that the life of 
these cells was intimately associated with the process of fermen- 
tation. Independently of Cagniard de la Tour, and almost simul- 
taneously, Schwann in Germany had published experiments which 
substantiated the former's suggestions. Following Gay-Lussac's 
work around 1835, it had been believed that the introduction of 
oxygen into a fermentable fluid was sufficient to initiate fermenta- 
tion or putrefaction. Schwann, on the contrary, showed that the 
production of alcohol and of yeast cells did not take place when 
grape fuice or other sugar solutions which had been boiled were 
brought into contact with air previously heated; some organic 
matter, preferably yeast, had to be added to the system to initiate 
the fermentation process. Schwann concluded from these findings 
that living microorganisms played an important part in fermenta- 
tion. To further support his belief, he tried to impede the produc- 
tion of alcohol by adding toxic substances to the fluid. Finding 
that mix vomica, so toxic to animals, did not retard fermentation, 
whereas arsenic interrupted it, he concluded that the living agents 
responsible for alcohol production were more plant than animal- 
like. He also confirmed Cagniard de la Tour's observations that 
the deposit produced during fermentation consisted of budding 
yeast cells, and he finally showed that fermentation commenced 
with the appearance of these yeast cells, that it progressed with 
their multiplication, and ceased as soon as their growth stopped. 
Another memoir on the same topic was published in 1837 by 
Kiitzing who, like Cagniard de la Tour, founded his opinions on 
microscopical observations; he recognized yeast as a vegetable 
organism and accurately described its appearance. According to 
him, alcoholic fermentation depended on the formation of yeast, 
which increased in amount whenever the necessary elements and 


the proper conditions were present for its propagation. *lt is 
obvious/' said Kiitzing, "that chemists must now strike yeast off 
the roll of chemical compounds, since it is not a compound but 
an organized body, an organism.*" 

These three papers were received with incredulity and Ber- 
zelius, at that time the arbiter of the chemical world, reviewed 
them all with impartial scorn in his Jahresbericht for 1839. He 
refused to see any value in the microscopical evidence and 
affirmed that yeast was no more to be regarded as an organism 
than was a precipitate of alumina. He criticized Schwann's experi- 
ments on the ground that the results were irregular and therefore 
did not prove anything concerning either the nature of yeast or 
the effect of heating on the presence or absence of fermentation. 
This criticism was justified to some extent by Schwamfs own 
honest confession that his results were not always predictable. 

To the scorn of Berzelius was soon added tihe sarcasm of Wohler 
and Liebig. At the request of the Academie des Sciences, Turpin 
of Paris had repeated in 1839 Cagniard de la Tour's observations 
and confirmed their accuracy. Stimulated by this publication, 
Wohler prepared an elaborate skit, which he sent to Liebig, who 
added to it some touches of his own and published it in the An- 
nalen der Chemie y following immediately upon a translation of 
Turpin's paper. Yeast was here described, with a considerable 
degree of anatomical realism, as consisting of eggs which de- 
veloped into minute animals shaped like distilling apparatus. 
These creatures took in sugar as food and digested it into carbonic 
acid and alcohol, which were separately excreted the whole 
process being easily followed under the microscope! 

The facts and theories presented by Cagniard de la Tour, 
Schwann, Kiitzing and Turpin to support the vitalistic theory of 
fermentation and putrefaction appear so simple and so compatible 
with the knowledge then available that it is difficult to understand 
why they did not immediately gain wide acceptance, but were 
instead neglected and even forgotten. It was not the difficulty of 
imagining the existence of microscopic living agents that proved 
an obstacle to the adoption of the vitalistic theory of f ermenta- 


Hon. Ever since 1675, when the Dutch lens grinder Leeuwenhoek 
had first shown their presence in water and in body fluids, micro- 
scopic organisms had often been seen by naturalists. Before Pas- 
teur's time, Christian Efarenberg, Ferdinand Cohn and other bot- 
anists had described and classified the bacteria microorganisms 
smaller than yeast, much harder to see and to study. 

Schwann's results were ignored because it was not always pos- 
sible to duplicate them. In particular, when he worked with infu- 
sions of animal tissues instead of simple sugar solutions, putrefac- 
tion often ensued when heated air was brought into contact with 
the heated infusion, a fact which seemed to prove that putrefac- 
tion could occur even in the absence of living agents. In 1843, 
Hermann Helmholtz, at that time a young medical student, and 
one who was to become immensely famous among the physiolo- 
gists and physicists of the century, made his scientific debut with 
a paper in which he concluded that putrefaction of nitrogenous 
substances was independent of germ life and that, even in alco- 
holic fermentation, germs probably occupied only a secondary 
and subordinate place. He was willing to grant only that putrid 
and fermentable materials possibly provided an attractive food 
substance to certain germs, and that when present, these germs 
might be capable of modifying to some extent the course of the 
fermentation and putrefaction processes, without being respon- 
sible for their initiation. 1 

There were other more profound reasons which made physi- 
ologists wary of accepting the vitalistic theory of fermentation 
and putrefaction. The belief that living things were the cause of 
these processes was in conflict with the Zeitgeist, the scientific 
and philosophical temper of the time. Mathematics, physics and 
chemistry had achieved so many triumphs, explained so many 
natural phenomena, some of them pertaining to the mystery of 
life itself, that most scientists did not want to acknowledge the 

1 This was merely a restatement of a view formerly expressed by Liehig: 
"As to the opinion which explains the putrefaction of animal substances by 
the presence of microscopic animalcula, it may be compared to that of a 
child who would explain the rapidity of the Rhine current by attributing 
it to the violent movement of the many millwheels at Mainz." 


need of a vital force to account for these commonly occurring 
processes. As fermentation could be described by a simple chem- 
ical reaction, it appeared pointless to explain it in terms of a 
living agent, instead of by the simple play of physical and chemi- 
cal forces. Little by little, science had expeled living forces from 
the domain of physiology and everyone believed that it was 
capable of pursuing this course even further; to appeal to a living 
agent as the cause of a chemical reaction appeared to be a back- 
ward step. In the kingdom of science, there were probably many 
who did not share the official optimism, and who did not believe 
that the time had come when everything could be accounted for 
in terms of known physicochemical forces. But the priests of the 
new faith Berzelius, Liebig, WoHer, Helmholtz, Berthelot and 
others were the supreme rulers of scientific thinking. The power 
of their doctrine and of their convictions, and the vigor of their 
personalities, smothered any voice that ventured to express an 
opinion in conflict with their own philosophy. As a reaction 
against the romantic and confused airings of the German Natur 
philosophi0 ? the new prophets had pronounced anathema on any- 
one who preached the doctrine of vitalism. 

Justus von Liebig, the dean of biochemical sciences, did not 
ignore the facts disclosed by Cagniard de la Tour, Schwann, Kiit- 
zing and Turpin. He was even willing to admit that yeast might 
be a small plant and that it played a secondary role in fermenta- 
tion. But he pointed out that in other decompositions of sugar, 
the lactic and butyric fermentations for example, nothing resem- 
bling yeast was to be found; nor had germs been seen participat- 
ing in the putrefaction of meat. If yeast then contributed to 
alcoholic fermentation, it was not as a living thing but only be- 
cause, on dying, it released in solution albuminoid material which 
imparted a vibration to the sugar molecule, a movement which 
caused it to break down into alcohol and carbonic acid. "The 
yeast of beer, and in general all animal and plant substances 
undergoing putrefaction, impart to other substances the state of 
decomposition in which they find themselves. The movement 
which is imparted to their own elements, as the result of the dis- 


turbance of the equilibrium, is communicated equally to the ele- 
ments of the substances which come in contact with them/* 

Liebig had no observed fact or theoretical basis to substantiate 
this description of the fermentation process. His hypothesis was 
a mere jumble of words, and Goethe could have well said of him: 

At the point where concepts fail, 

At the right time a word is thrust in there. 

With words we fitly can our foes assail, 

With words a system we prepare. 

Words we quite fitly can believe, 

Nor from a word a mere iota thieve. 

However, Louis Thenard had made an observation which ap- 
peared compatible with Liebig's argument. He had seen that, by 
adding twenty grams of yeast to one hundred grains of cane sugar 
in solution in water, a rapid and regular fermentation was ob- 
tained > after which the remaining yeast, collected on a filter, 
weighed only thirteen grams. Added to a new quantity of pure 
sugar solution, this residual yeast produced fermentation more 
slowly than the original yeast, after which it was reduced to ten 
grams and became even less capable of causing the fermentation 
of sugar. This appeared as proof that yeast destroyed itself in the 
course of its own fermenting activity. 

It does not appear profitable to pursue the complex structure 
of all the arguments which brought Liebig's views to the status 
of official dogma. Vague as it was, his theory agreed with the 
spirit of the age and served to incorporate the phenomena of fer- 
mentation and putrefaction into the fold of the physicochemical 
doctrine. To overcome the theory, it was not sufficient to oppose 
facts to facts, and interpretation to interpretation; it was necessary 
to bring to battle enough energy, talent and conviction to chal- 
lenge and override the entrenched official position. 

As a fighter, Pasteur proved more than a match for Liebig. 

There is no indication that Pasteur had given any systematic 
thought to the problem of fermentation before he arrived in Lille. 
The first entries in his laboratory notebooks of experiments deal- 


Ing with this subject date from September 1855, and yet, by 
August 1857, lie was ready to present before the Soci^te des 
Sciences de Lille, in Ms Memoire sur la fermentation appelee 
lactique, a complete statement of the germ theory with a proposed 
methodology of experimentation. Unfortunately, few facts are 
available to account for this magnificent intellectual performance, 
to reveal in particular how he overcame, in his own mind, the 
pressure of authoritative scientific opinion and came to adopt a 
biological interpretation for a phenomenon which was described 
in all textbooks as a chemical reaction. 

Even though trained as a chemist, Pasteur always had an eye 
for the biological implications of his work. As early as 1854, for 
example, after observing that the part of a crystal which has been 
damaged grows faster than the other parts, as if with the purpose 
of restoring the integrity of crystalline structure, he stated that 
this phenomenon was analogous to ""those exhibited by living 
beings which have received a wound. The part which has been 
damaged slowly recovers its original form, and the process of 
tissue growth is, at this point, much more active than under 
normal conditions." We have also emphasized in the preceding 
chapter how possessed he was by the thought that molecular 
asymmetry is related to living processes. The expression "The 
great problem of Me . . /* often appeared, in one sentence or 
another, in letters to his friend Chappuis or to his father, or in 
his lectures and notes. This unusual concern with the ultimate 
nature of living phenomena accounted in part for his receptive- 
ness to any fact susceptible of a vitalistic interpretation. 

The production of optically active molecules, in particular of 
optically active amyl alcohol, seems to have been the specific 
fact that led him to regard fermentation as brought about by 
living agents. Amyl alcohol, a well-known product of distillation, 
had been the first exception which he had encountered to the 
correlation between asymmetry in crystal structure and optical 
activity, and he had studied it with especial care. The manner in 
which this study launched him into the analysis of yeast fermenta- 
tion with a preconceived idea opposite to Liebig's doctrines is 


clearly set forth in Ms own writings. Lieblg assumed that the op- 
tical activity of amyl alcohol was a consequence of the asym- 
metry of the sugar, from which it was derived during fermenta- 
tion; Pasteur on the contrary felt convinced that the molecule of 
amyl alcohol was too remotely related to that of sugar to have 
preserved the asymmetry of the latter. **Every time/' he says, 
"that we try to follow the optical activity of a substance into its 
derivatives, we see it promptly disappear. The fundamental 
molecular group must be preserved intact, as it were, in the de- 
rivative, in order for the latter to be optically active. . . , The 
molecular group of amyl alcohol is far too different from that of 
the sugar, if derived from it, to retain therefrom an asymmetrical 
arrangement of its atoms." In consequence, Pasteur regarded the 
asymmetry of amyl alcohol as due to a new creation, and such 
creation of an asymmetric molecule wag, according to him, pos- 
sible only through the intervention of life. As a corollary, fermen- 
tation had to be a vital process, and not the purely chemical 
transformation which Liebig assumed it to be. 

Although Pasteur worked intensively on alcoholic fermentation 
through 1855 and 1856, his first communication on the germ 
theory dealt primarily with the conversion of sugar into lactic 
acid, the reaction which is responsible for the souring of milk. 
The selection of this subject to introduce the new doctrine is the 
more surprising because lactic acid fermentation is less impor- 
tant than alcoholic fermentation from the industrial point of 
view, was then less well known scientifically, and had less his- 
torical glamour. It appears possible that Pasteur's choice was 
dictated in part by a shrewd sense of the strategy best adapted 
to the defeat of Liebig's chemical theory. Alcoholic fermenta- 
tion had already lost its bloom, for Liebig and his partisans 
were willing to regard yeast as a living organism. Their great 
argument was always: What role can you attribute to yeast, 
when so many other related fermentations, the lactic fermen- 
tation for example, take place without the presence of anything 
which resembles it? ... In a certain sense, therefore, lactic fer- 
mentation was the champ clos In which the battle had to be 


fought Another reason may also have influenced Pasteur. Of all 
fermentations, none is simpler chemically than the conversion of 
sugar into lactic acid. Essentially it involves the breakdown of 
one molecule of sugar into two halves which are the lactic acid 
molecules. If it could be shown that this simple process was 
really carried out by a living agent, then, reasonably, it would 
become unnecessary to fight, one after the other, all the battles 
of the individual fermentations. Lactic acid fermentation could 
rightly serve as a general pattern for this class of phenomenon. 

In reality, Pasteur's Memoire sur la fermentation appelee 
lactique does not offer a rigorous demonstration of the germ 
theory. It states only that the gray material deposited during the 
conversion of sugar into lactic acid does, in its mode of forma- 
tion and in many of its properties, present some analogy to yeast. 
If a bit of this gray deposit is added to a new sugar solution, it 
increases in amount as lactic acid is produced. Like yeast, this 
lactic ferment has also an organized shape, although it is dif- 
ferent, smaller and more difficult to see. To make yeast grow, 
it is the practice to add an albuminoid material to the fermenting 
sugar; similarly more rapid production of lactic acid, accom- 
panied by more rapid and abundant production of the gray de- 
posit, is assured if one adds some albuminoid material to the 
sugar solution along with the lactic ferment. Whereas Liebig and 
his school regarded the albuminoid material as the ferment itself, 
Pasteur claimed it was nothing but food for the yeast, or for the 
lactic ferment, both of which needed it to grow and thereby to 
cause the fermentation. 

Side by side with these affirmations concerning the vital nature 
of the fermentation process, Pasteur described in the same short 
memoir a methodology which even today forms the basis of bac- 
teriological technique. He showed that one can grow the ferment 
in a clear nutrient bouillon, where it multiplies to give rise to a 
population of microscopic living beings, all the individuals of 
which resemble one another. Once grown in adequate amount, 
and in the pure state, it accomplishes with extraordinary rapidity 
the chemical transformation over which it presides, namely the 


production of lactic acid. The memoir presents, also, an exact 
statement of the influence of the acidity, neutrality, or alkalinity 
of the liquid on the course of fermentation. Whereas yeast pre- 
fers acid media, the lactic ferment grows best at neutrality; and 
it is for this reason that the lactic fermentation is favored by the 
addition of chalk to the sugar solution. There is also a hint, as it 
were an omen, of the effect of antiseptics. "The essential oil of 
onion Juice completely inhibits the formation of the yeast of beer; 
it appears equally harmful to infusoria. It can arrest the develop- 
ment of these organisms without having any notable influence 
on the lactic ferment." Antiseptics, then, can be used for separat- 
ing the different ferments one from the other. 

The idea of a specific ferment associated with each fermenta- 
tion, of disproportion between the weight of the ferment pro- 
duced and the weight of matter transformed, of vital competition 
between two organisms which simultaneously invade the same 
medium, resulting in the dominance of the one best adapted to 
the culture conditions all these ideas, which the future was to 
develop so thoroughly, are found clearly set forth in this paper. 
Its fundamental spirit can be summarized in Pasteur's own 
words: "The purity of a ferment, its homogeneity, its free un- 
restrained development by the aid of food substances well 
adapted to its individual nature, these are some of the conditions 
which are essential for good fermentation." 

It is a remarkable fact that this preliminary memoir, which 
presented in such specific terms the credo and the ritual of the 
new doctrine, has stood the strain of all subsequent experimen- 
tation without showing any defect. And yet, its claims were pre- 
sented without unequivocal evidence. Indeed, the criteria as to 
what constitutes evidence for the causal participation of a liv- 
ing agent in a chemical or pathological process are so ill-defined, 
even today, that the history of microbiology offers countless 
examples of claims of etiological causation which subsequent ex- 
perience has failed to verify. Pasteur himself was well aware of 
this difficulty, and stated at the end of his memoir, "If anyone 
hould say that my conclusions go beyond the established facts, 


I would agree, in the sense that I have taken my stand un- 
reservedly in an order of ideas which, strictly speaking, cannot 
be irrefutably demonstrated." 

Pasteur's claims did not deal with the ultimate nature of the 
fermentation process. They only expressed the view that, under 
the conditions used by Lavoisier, Gay-Lussac, Thenard and 
Liebig, the formation of lactic acid, of alcohol, of butyric acid 
of all products of fermentation was always dependent upon 
the life of yeast or of bacteria. Fermentation was, as he said, 
"correlative with life." In consequence, the further understand- 
ing of the fermentation process demanded a knowledge of the 
conditions which affect the life of the germs and their physio- 
logical activities. The demonstration that ferments were living 
germs was the first problem that had to be solved before a fol- 
lowing generation could undertake the detailed analysis of the 
composition of these germs, of their enzymatic equipment, of 
the specific chemical reactions for which they are responsible. The 
specificity of enzymes and their mode of action is to our age 
what the specificity of germs and the conditions of their life was 
to the middle of the nineteenth century. Pasteu/s role was to 
define the problem of fermentation in terms that were scien- 
tifically meaningful for his time.; Such a limited scope may not 
be sufficient for the philosopher, but the experimenter has to be 
satisfied with it, for as is said in Ecclesiastes: "To every thing 
there is a season, and a time to every purpose . . ." 

Although the Memoire sur la fermentation appelee lactique was 
the Manifesto of the germ theory, it was only in the Memoire sur 
la fermentation alcoolique, published in its preliminary form in 
1857 and in extenso in 1860, that Pasteur summoned the experi- 
mental evidence which demonstrated the participation of living 
agents in the phenomena of fermentation. 

It was by then generally accepted that yeast was a necessary 
accompaniment of alcoholic fermentation, but a few workers still 
doubted that it was a living, organized structure. Berzelius con- 
sidered yeast as some amorphous organic material, precipitated 


during the fermentation of beer and mimicking the morphology 
of simple plant life; but mere form, Berzelius pointed out, does 
not constitute life. Even those who were willing to regard yeast 
as a microscopic plant believed, with Liebig, that it induced 
fermentation not as a living agent, but because its death liberated 
into the sugar solution albuminoid material which imparted a 
molecular vibration capable of breaking down the sugar mole- 
cule into alcohol and carbon dioxide. Pasteur finally demolished 
this thesis, by two independent lines of evidence. He showed 
that the products of alcoholic fermentation are more numerous 
and complex than indicated by the simple terms of Lavoisie/s 
chemical formula; and he succeeded in causing fermentation 
to occur in a purely mineral medium, under conditions where 
fermentative activity and yeast multiplication went hand in hand. 

Unimpressed by the authority of tradition, Pasteur first estab- 
lished that, in addition to the alcohol and carbon dioxide de- 
manded by the classical formula of alcoholic fermentation, there 
are produced significant amounts of other substances such as 
glycerine, succinic acid, amyl alcohol. It was, he pointed out> 
because the supporters of the chemical theory of fermentation 
were prejudiced in favor of a simple reaction that they had 
neglected to look for these substances, which are always present. 

Although the multiplicity of these side products several of 
them optically active made it plausible that fermentation was 
a complex process due to the agency of life, this did not prove 
the vitaKstic theory. In order to link the production of alcohol 
and the multiplication of yeast by a cause-effect relationship, 
Pasteur undertook an experiment which, for the time, was as 
bold and original in its concept as it appears today simple and 

Liebig had supported his view that yeast produces alcohol 
only after its death and when undergoing decomposition by 
quoting the experiment in which Thenard had found that the 
weight of yeast decreased during fermentation. Liebig also em- 
phasized that ammonia is often released by yeast as it decom- 


poses while fermenting the sugar. These statements were based 
on correct observations, and described facts which were of com- 
mon occurrence in those days when, unknown to the investigators, 
yeast fermentation often took place with the presence of con- 
taminating bacterial growth. These observed facts made it there- 
fore not illogical to conclude that fermentation and the death 
of yeast were causally related. Unfortunately, logic is an un- 
reliable instrument for the discovery of truth, for its use implies 
knowledge of all the essential components of an argument in 
most cases, an unjustified assumption. Nor is the experimental 
method the infallible revealer of pure and eternal fact that some, 
including Pasteur, would have us believe. The validity of a theory- 
is usually proven more by its consequences than by conscien- 
tious effort and brilliant intellect. The observations quoted by 
Liebig were correct, but the very fact that yeast is a living 
plant had introduced so many complicating and unknown factors 
in the experiments that some of the most significant facts of 
the reaction had escaped him. It is because Pasteur had intuitively 
guessed the true nature of fermentation that he was able to find 
the flaw in Liebig's intellectual edifice and to arrange conditions 
for demonstrating that alcohol was a product of the life of yeast 
Armed with his conviction, Pasteur was bold enough to reverse 
Liebig's reasoning and to arrange his own experiments in such a 
way that, instead of ammonia being given off during fermentation, 
the yeast would be produced from ammonia added to the mixture. 
Technically, the problem was to grow the yeast in a nutrient 
liquid devoid of organic nitrogen a liquid containing only 
sugar, ammonia to provide nitrogen, and some mineral salts to 
supply the yeast globules with their structural elements. Pasteur 
had the ingenious idea of adding also to his nutrient medium the 
ashes of incinerated yeast in addition to the salts of phosphoric 
acid, potassium, magnesium and iron, hoping to supply thereby 
the unknown mineral elements required by the small plant. He 
had to acknowledge that, even under these conditions, yeast 
grew less readily than in the juice of the grape or in beer brew, 
probably because it had to synthesize all its tissue constituents 


instead of finding many of the metabolic factors ready-made in 
the natural organic fluids. Nevertheless, he could report in 1860 
that he had obtained fermentation in his synthetic medium 
inoculated with minute amounts of yeast, and that the amount 
of alcohol produced ran parallel with the multiplication of the 
yeast. Realizing that this was the crucial test of his thesis, he 
returned to it over and over again. By perfecting the medium and 
employing a more vigorous strain of yeast, he succeeded in ob- 
taining more rapid fermentation by a technique which he de- 
scribed in the Etudes sur la Bi&re in 1876. This momentous experi- 
ment established once and for all that, contrary to Liebig's claims, 
organic material in decomposition is not necessary to start alco- 
holic fermentation. An imperceptible trace of yeast, introduced 
Into a liquid containing only sugar and mineral salts, makes the 
sugar ferment while the yeast develops, buds and multiplies. All 
the carbon of the new yeast globules is derived from the sugar; 
all their nitrogen from the ammonia. 

What, then, was the meaning of that odd experiment in which 
Thenard had found that the amount of yeast decreases when large 
amounts of it are added to a sugar solution to make it ferment? 
That meant, according to Pasteur, that many of the old yeast 
globules died in a sugar solution depleted of nitrogen and min- 
erals. In breaking down, they released into solution some of their 
own cellular constituents which were then used by the new 
young globules to multiply and to ferment the sugar. There were 
not enough new yeast globules formed to balance the loss of 
weight in the old ones due to the dissolution. However, if the 
weight of the organic matter which had gone into solution was 
added to that of the formed yeast, then the total weight was 
found to increase during fermentation, because there is always 
a little sugar which is transformed into yeast. Thus, whatever the 
conditions employed, whether the ferment was introduced into 
synthetic mineral media, or into fluids rich in organic matter 
derived from grape, from barley, or from the decomposing yeast 
itself, the production of alcohol was always dependent upon the 
life of yeast. And Pasteur concluded his 1860 memoir with these 


Incisive and uncompromising words: "Alcoholic fermentation is 
an act correlated with the life and with the organization of these 
globules, and not with their death or their putrefaction. It is not 
due to a contact action in which the transformation of the sugar 
is accomplished in the presence of the ferment without the 
latter giving or taking anything from it." These were the very 
words with which he had ended Ms preliminary announcement 
of the genn theory of lactic fermentation in 1857. Subsequent 
experimentation had served only to add evidence to the conclusion 
which he had intuitively reached at the beginning of his studies. 

Pasteur now returned to the lactic acid fermentation and here 
again succeeded in causing it to proceed in a simple medium. 
Although the lactic ferment was smaller than that of yeast, its 
needs were not less, only different. Like yeast it had its own 
specific requirements, as all living things have. 

Within a few years, the generality of the view that ferments 
are living beings was established. Pasteur himself showed that 
the germs responsible for the production of tartaric, butyric and 
acetic acids could be readily cultivated in synthetic media. Each 
one of these germs was a living microorganism, characterized by 
a definite morphology, definite nutritional requirements and sus- 
ceptibilities to toxic influences, as well as by the ability to carry 
out a specific type of biochemical performance. Raulin, the first 
of Pasteur's assistants, added weight to the new doctrine by defin- 
ing with unsurpassed completeness and precision the growth 
requirements of the mold AspergiUus niger, and by revealing the 
influence of nutritional factors, and particularly of rare mineral 
elements, in the life of microorganisms. 

One cannot exaggerate the importance of these studies for the 
evolution of biochemical sciences. As early as 1860, Pasteur him- 
self pointed out that the findings made in his laboratory would 
permit physiology to attack the fundamental chemical problems 
of life. The bodies of plants and animals consist of an immense 
number of cells, whereas in microorganisms, the living agent is 
reduced to the single-cell level. By studying microbial physiology, 


therefore, It became possible to analyze the chemical phenomena 
which determine the function of the individual cell the fun- 
damental unit of life - be it that of a plant, a microorganism, an 
animal, or even a man. 

By 1859 Pasteur had sufficiently mastered the techniques of 
pure culture and of preparation of selective media to be able to 
bring about at will one or another type of fermentation, and to 
determine its causative agent and its chemical mechanism. For 
example, when he added to a solution containing a salt of lactic 
acid a drop of a liquid undergoing butyric acid fermentation, 
there soon ensued a transformation of the lactic acid into butyric 
acid, with evolution of a gas consisting of a mixture of carbon 
dioxide and hydrogen. Simultaneously with the new chemical 
process, a new microscopic population appeared in the fluid. 
It consisted of short rods which, curiously enough, moved rapidly 
to and fro with undulating movements. Because of the view then 
prevalent that motility was one of the differential characteristics 
between the animal and plant kingdoms, Pasteur was at first 
inclined to regard these motile beings as minute animals, and 
for this reason, he referred to them as "infusoria/' For this reason 
also, he was for a while reluctant to believe that they could be 
the real cause of butyric acid fermentation as this activity was 
universally considered more plant- than animal-like. "I was far 
from expecting such a result," said he; "so far, indeed, that for 
a long time I thought it my duty to try to prevent the appearance 
of these little animals, for fear they might feed on the micro- 
scopic plants which I supposed to be the true butyric ferment, 
and which I was trying to discover. . . . Finally, I was struck by 
the coincidence which my analyses revealed between the infusoria 
and the production of this [butyric] acid." 

Pasteur's hesitation in accepting a motile microorganism as the 
cause of butyric acid fermentation, because motility was thought 
to be the prerogative of animal life, illustrates the range of diffi- 
culties which he had to overcome in defining the place of nri- 
crobial life in natural processes. Within a few years, his own 


studies on anaerobic metabolism were to show that there exist 
many chemical reactions which are common to all types of life. 
But in I860, biologists and biochemists had not yet realized that, 
at the microscopic level, animal and plant life merge and cannot 
be differentiated by any simple criteria. Moreover, Pasteur was 
not a naturalist, and he was working alone, without the support 
of a scientific tradition, without associates who could share his 
doubts and his surprises at the unexpected phenomena that he 
was discovering wherever he turned. The many and brief ac- 
counts of new observations which occur repeatedly throughout 
his writings leave the impression of a child running to and fro 
in a forest, overwhelmed with a sense of wonder at the signs of 
unknown life which he sees or only perceives, intoxicated at dis- 
covering the diversity of the Creation. Butyric acid fermentation, 
which so disturbed him by revealing intense motility in microbial 
life, also led him to discover new and unexpected forms of bio- 
chemical processes and a new liaunt of life. 

Life in the absence of air leaped, so to speak, into his field of 
vision while he was examining under the microscope a drop of 
fluid undergoing butyric fermentation. It was his practice to take 
a drop, place it on the glass slide, cover it quickly with a cover 
slip, and examine the preparation through the microscope. While 
examining, with the care that he applied to everything, one of 
these little flattened drops of liquid undergoing butyric fermen- 
tation, he was astonished to see that the bacteria became non- 
motile on the margins of the drop although they continued to 
move with agility in the central portion. This was a spectacle 
quite the reverse of that which he had observed in the case of 
other infusions in which the animalcules often left the central 
portions of the drop to approach the margin, the only place where 
there was enough oxygen for all. In the presence of this observa- 
tion, he asked himself whether the butyric microorganisms were 
trying to escape from the oxygen; and he soon found that it was 
indeed possible to retard or even arrest butyric fermentation 
by passing a current of air through the fermenting fluid. Thus 
was introduced into science the idea that there exists a form of 


Me which can function in the absence of oxygen, although this 
gas had until then been believed to be an essential requirement 
of aH Hying creatures. We shall see how Pasteur developed this 
idea later. For the moment, we must be content with saluting its 

To facilitate discussion of the problem, Pasteur devised the 
words "aerobic* and "anaerobic" to designate respectively Me 
in the presence and in the absence of oxygen. How could the 
anaerobic beings, which fear oxygen, live and multiply under 
natural conditions in the culture broths of the laboratory, which 
were all in contact with the oxygen of air? Without hesitation 
and without proof, Pasteur guessed that he had introduced into 
his cultures, along with the anaerobic butyric ferment, other 
microscopic germs which could use up the oxygen in solution and 
form on the surface of the fluid a film of growth below which the 
gaseous environment became compatible with anaerobic life. 
On the basis of limited observations, and without extensive ex- 
perimental evidence, he also became convinced that similar 
phenomena occur during putrefaction, and that the evil-smelling 
decomposition of beef bouillon, egg albumin, or meat is the result 
of the anaerobic life of specialized germs that attack proteins 
under the protection of aerobic forms capable of removing the 
oxygen from the environment. He soon arrived at the view that 
gas production during butyric fermentation and putrefaction is 
the manifestation of life in the absence of oxygen, and he sus- 
pected an intimate relationship between fermentation processes 
and anaerobic Me. Several years were to elapse, however, before 
he could define these problems in terms concrete enough to give 
them a clear meaning. 

Pasteur never attempted to work out in detail the mechanisms 
by which nitrogenous organic matter is destroyed during putre- 
faction. He probably judged that this process was too complex 
and obscure from the chemical point of view to lend itself to 
elegant experimental analysis. He chose instead the production 
of vinegar to illustrate further the activities of microorganisms. 


Vinegar production was then weU known to result from tlie 
oxidation of alcohol to acetic acid. In the French process, as 
practiced in Orleans, alcohol was allowed to undergo slow oxida- 
tion in casks standing on end in piles, and about two-thirds full 
of a mixture of finished vinegar and new wine. In the German 
process, the vinegar was made from a weak alcohol solution, to 
which was added some acetic acid and some acid beer or sharp 
wine, or other organic matter in course of alteration; this mixture 
was poured over a hollow column several meters high, containing 
loosely piled beech shavings, and was alowed to trickle down 
slowly against an upward current of air. 

The German vinegar process appeared to be readily explained 
in terms of chemical theories based on the catalytic oxidation 
of alcohol in the presence of platinum. Concentrated alcohol al- 
lowed to fall on finely divided platinum is spontaneously oxidized 
to aldehyde and acetic acid, with production of much heat. Al- 
though platinum is not altered in the course of the process it ac- 
tivates the reaction between oxygen and alcohol, thus behaving 
in Berzelius's terminology as a true catalyst. Liebig, therefore, 
appeared to be on firm ground when he assumed that other oxi- 
dation processes occurring in nature the oxidation of ammonia 
to nitrate in soil, or the oxidation of drying oils such as linseed 
oil, for example were the outcome of similar reactions, utiliz- 
ing catalysts other than platinum. In the case of vinegar making, 
he considered that the beech shavings simply played more eco- 
nomically the role of platinum. Like platinum they seemed to 
act by their mere presence, being still intact and effective after 
ten to twenty years of use. The acid beer or sharp wine added 
to the alcohol mixture was there, according to Liebig, merely to 
set the process in motion. The reasoning by which Liebig be- 
lieved he had demonstrated the mechanism of the formation of 
acetic acid in the German vinegar industry appeared very con- 
vincing. In his words: "Alcohol, when pure or diluted with water, 
does not change to acid in the presence of air. Wine, beer . . . 
which contain foreign organic matter in addition to alcohol, 
slowly become acid in contact with air . . . Dilute alcohol under- 


goes the same transformation when one adds to it certain organic 
matter, as germinated barley, wine ... or even ready-made 
vinegar. . . . 

There cannot be any doubt concerning the role of nitrogenous 
substances in the acidification of alcohol They render it capable 
of absorbing oxygen, which alone, by itself, cannot be absorbed. 
The acidification of alcohol is absolutely of the same order as 
the formation of sulfuric acid in the lead chambers; just as oxy- 
gen is fixed on sulfurous acid through the intermediary agency 
of nitrous oxide, similarly the nitrogenous substances, in the pres- 
ence of acetic acid, absorb oxygen in such manner as to render 
it susceptible of being fixed by alcohol. . . . When wet, wood 
shavings absorb oxygen rapidly and rot . . . This property of 
absorbing oxygen remains when the shavings are wetted with 
dilute alcohol, but in this case, the oxygen is carried over to 
the alcohol instead of to the wood, thus giving rise to acetic 

Despite its simple and logical appeal, Liebig's theory was 
wrong. It was based only on analogy and logic, but Nature, as if 
to humble man, demands that he return every time to firsthand 
experience if he wishes to discover the truth. Analogy and logic 
provide exhilarating intellectual entertainment, but they rarely 
constitute dependable guides for the exploration of reality. 

In the Orleans vinegar process, there is produced on the sur- 
face of the liquid in the casks which behave properly a fragile 
pellicle known as "mother of vinegar," which the vinegar maker 
takes great pains not to disturb and not to submerge, because he 
considers it a precious ally. Experience having taught that the 
pellicle needs air for its development, windows are open at the 
top of the cask, above the surface of the liquid. Vinegar making 
goes well as long as the pellicle remains spread over the surface 
of the liquid, but stops if it is broken and falls to the bottom. It is 
then necessary to produce a new mother of vinegar to start the 
process again. 

As early as 1822, Persoon had suspected the living nature of 
the "mother of vinegar" and had given to it the name "myco- 


denna" to suggest its plant nature. In 1837, Kiitzing had even 
seen the bacterial cells which constitute the mycoderma skin and 
had postulated a connection between the life of the bacteria and 
the production of vinegar. Similarly Thompson in 1852 had stated 
his conviction that the production of acetic acid was due to the 
"vinegar plant." But here, as in the case of the relation of yeast 
to alcoholic fermentation, the authority of Berzelius, Wohler and 
Liebig had squelched the voice of those who were trying to bring 
life back into an area which chemistry believed it had conquered. 
And here again, it was Pasteur who dared to challenge Liebig's 
autocratic mandate and conjure the experimental evidence on 
which was established the vitalistic theory of acetic acid fer- 

Pasteur convinced himself that, in the Orleans process as well 
as in laboratory reactions, the conversion of wine into vinegar 
depended upon the development of a thin layer consisting of 
microscopic bacteria named Mycoderma aceti which were capable 
of floating on the surface of the fluid because of their fatty nature. 
Moreover, he found that minute amounts of the Mycoderma, 
transferred to a synthetic solution containing dilute alcohol, 
ammonia, and mineral salts, increased in abundance, and simul- 
taneously produced acetic acid. He also detected a barely visible 
film of the same Mycoderma aceti on the surface of the wood 
shavings used in the German process. New shavings, or active 
shavings which had been heated to destroy the Mycoderma pres- 
ent on their surface, were found by *hfrn to be unable to convert 
alcohol into acetic acid, however slow the flow of alcohol over 
them. Neither did alcohol fix oxygen when allowed to flow along 
a clean rope, but as soon as the shavings or the rope were wetted 
with a fluid containing the Mycoderma, alcohol was converted 
into acetic acid as in the towers of beech shavings. 

These observations were of great practical importance in giv- 
ing a rational basis to vinegar manufacture, and Pasteur was thus 
led to advocate modifications of the time-honored industrial 
procedures. In 1864, he was asked to outline his new method in 
a speech before the Chamber of Commerce of Orleans. There, in 


simple, precise, and clear words, he presented the theoretical 
basis of his concept and its practical applications. 

Mycoderma aceti, he pointed out, will grow best at fairly high 
temperatures, and for this reason the transformation of wine 
into vinegar occurs most rapidly in rooms heated at 15-20 C. 
Mycoderma needs nitrogenous materials, phosphates of magne- 
sium and potassium, and other nutrients. It is most active at 
acidic reaction, a property that explains the practice of adding 
preformed vinegar to wine before starting the manufacture. 
These exacting requirements account for the fact that Mycoderma 
aceti is not capable of converting pure alcohol diluted with water 
into acetic acid, as this fluid lacks the nutritional elements re- 
quired for growth. For this reason a little sharp wine, or acid 
beer, or other organic matter, is added to the dilute alcohol solu- 
tion used in the German process before allowing it to trickle down 
the hollow column of beech shavings. This organic matter is not 
added to act as a ferment and set the phenomenon in motion as 
thought by Liebig, but only to serve as food for the Mycoderma. 

The oxidation to acetic acid of ten liters of alcohol requires 
more than six kilograms of oxygen, which has to be supplied by 
more than fifteen cubic meters of air. It is the role of Mycoderma 
aceti to transfer this oxygen from the air to the alcohol. Any agent 
or condition interfering with this oxygen transfer, which takes 
place through the surface pellicle of the mother of vinegar, also 
interferes with the production of acetic acid, and Pasteur made 
clear to the vinegar manufacturers that many of their failures 
could be explained in these terms. 

When the Mycoderma pellicle falls to the bottom of the vat 
and is submerged, it becomes unable to convert alcohol into 
acetic acid. On the other hand if the supply of oxygen is too 
abundant and the concentration of alcohol too low, the Myco- 
derma destroys the formed acetic acid by oxidizing it further to 
carbon dioxide and water. 

The precise understanding of the mechanism by which wine 
is converted into vinegar had immediate practical consequences. 
Knowing the living nature of the "mother of vinegar" and its 


physiological requirements, the vinegar makers no longer had 
to submit blindly to its heretofore unpredictable vagaries. Instead 
of depending upon the spontaneous but slow and erratic appear- 
ance of the Mycoderma pellicle on their vats, they became its 
master and could sow it on the surface of the fluid. The tra- 
ditional method made it necessary to keep the fermentation going 
by constantly feeding more wine to the casks, lest the Mycoderma 
veil should sink to the bottom, become starved for oxygen, and 
lose its activity. By hastening or retarding growth at will, the 
producers could now make the process more dependable, easier 
to control and could adjust the production of vinegar to the de- 
mands of the market. Biological science had found its place in 
industrial technology. 

In 1866, Pasteur published a book entitled Etudes sur le vin, 
ses maladies, causes qui IBS provoquent. Precedes nouveaux pour 
le conserver et pour le vieillir. 2 He came from a wine-producing 
district, and had much to say concerning the factors affecting the 
taste, appearance, and nutritive qualities of the beverage. 

As everyone knows, aging alters the properties of wine, in- 
creasing its mellowness, decreasing its opacity, changing its color. 
Whereas all young wines are raw and thick, a properly aged wine 
acquires refinement and sometimes distinction. On the other 
hand, wine can lose completely its strength and character if the 
aging process is carried too far. Pasteur therefore asked himself 
the question, what goes on in a wine that becomes old normally, 
in the absence of disease microorganisms, and how can the aging 
process be controlled? 

Practical wine makers as well as chemists had always been con- 
vinced that uncontrolled access of air was detrimental during the 
making of wine. Chemical analysis revealed that oxygen dis- 
appeared rapidly from the atmosphere with which wine was in 
contact in casks or bottles. As admission of more air was often 
associated with loss of quality, concomitantly with absorption of 

2 Studies on Wine. Its Diseases; Causes that Provoke Them. New Pro- 
cedures to Preserve It and to Age It. 


oxygen, it appeared to be a justifiable conclusion that spoiling of 
the flavor was a result of oxidation. In consequence, care was 
taken throughout the operations of wine making to expose the 
wine to the air only so long as absolutely necessary for the de- 
canting. Pasteur showed that the role of air in the aging of wine 
is in reality a very complex one and consists of at least two inde- 
pendent effects. On the one hand, oxygen exerts an adverse effect 
on quality by encouraging the growth of certain contaminating 
microorganisms. On the other hand, when acting alone, free 
from any microbial action, oxygen may have a beneficial effect. 
It takes away the acidic and rough taste of new wine, rendering 
it more fit to drink; it precipitates slowly some of its dark color- 
ing matter, giving it finally the onionskin tint, so praised when 
the right degree has been achieved. Oxygen brings about the 
quality of old wine, but if its aging action is allowed to proceed 
too far, it ends by spoiling the very wine which it first improved. 

Pasteur devised simple experiments to illustrate the relation of 
oxygen to the aging of wine. 

Suppose that wine saturated with carbon dioxide is introduced 
into a glass bottle so as to fill it completely, under such pre- 
cautions that the liquid never comes into contact with air; sup- 
pose also that the bottle is sealed hermetically with wax. Such 
a wine will preserve its original color and savor; it will not age 
and will remain raw new wine, because glass and wax protect 
it completely from the access of air. If, however, the bottle is 
left half empty and merely stoppered with an ordinary cork, a 
significant degree of gas exchange takes place through the cork, 
and oxygen slowly gains access to the wine. An amorphous de- 
posit consisting of the red coloring matter appears slowly, and 
the flavor simultaneously changes. The wine may even fade com- 
pletely in color and in flavor if the amount of air in the 
bottle is too high. 

Perusal of all the pages that Pasteur devoted to the aging 
process leaves little doubt that he greatly enjoyed studying the 
factors affecting the quality of wines. The Etudes sur le vin 
describe extensive use of chemical techniques in determining 
the concentration of alcohol, glycerine, tartaric acid, succinic acid, 


gums, and sugar present in the wine, and in following the changes 
in the composition of air exposed to it. New and old methods of 
wine making are discussed in great detail, either because they 
bear a relation to the problem at hand, or merely for the sake of 
interest Thus, we learn that in certain regions it used to be the 
practice to stir the crushed grapes vigorously, before fermenta- 
tion, in order to achieve in advance a form of aging of the wine. 
Pasteur also mentions his habit of discussing with peasants their 
empirical procedures in an attempt to find a rational basis for 
their time-honored practices. 

"In all countries and all epochs, as appears from the writings 
of the Latin agronomists, wine makers have recognized a rela- 
tion between the lif e of wine and that of the grapevine. They pre- 
tend that when the grape flowers, around June 15 in the Jura, 
wine is in travail, and again in August, when the grape begins 
to ripen. They are inclined to believe that there exists some mys- 
terious correlation between these circumstances. In reality, these 
are the periods when variations occur in the temperature of the 
cellars, and the changes in fermentative activity probably find 
their explanation in these changes of temperature. But what does 
it matter if the peasants credit a myth? It is only the fact itself 
that we need consider, because it serves as a guide in certain 
practices of vinification. 

"The most ancient writings recommend that the first draining- 
off be done in the month of March, when the north wind blows 
and not the south wind, which, is the wind of rain, at least in the 
Jura. Do not dismiss the practice as prejudice. ... In my opin- 
ion, it has a rational basis. Wine, especially young wine, is super- 
saturated with carbon dioxide. If the barometric pressure is very 
low for several days, wine will let the gas escape. There will arise 
from the bottom of the casks small bubbles which carry up with 
them some of the fine deposit. The wine will then be less clear 
than if we draw it off on a day when the barometric pressure tends 
to increase the solubility of gases in liquids. . . !' 

As a wine maker of Arbois had assured him that the north wind 
affected both wine and the water of the river La Cuisance, Pas- 
teur made haste to look for an explanation. 


The river Cuisance which goes through Arbols has its source 
a few miles away in a chalky country. Its water is loaded with 
calcium carbonate dissolved by virtue of the carbon dioxide that 
it contains. On rainy days, the river water becomes less lim- 
pid. . . . Sometimes the moss in its bottom is seen to raise. On 
the contrary, let the north wind blow, and one can see a needle 
at a depth of several feet Does not this confirm the explanation 
which I just gave you concerning the advisability of drawing the 
wine by the north wind?** 

Despite Pasteur's obvious interest in the varied technological 
aspects of wine making, the most important part of this book 
deals with the study of microorganisms which interfere with the 
normal course of fermentation. 

Under natural, that is, uncontrolled conditions, the different 
fermentation processes often give rise to undesirable products. 
For example, acidification may occur where it is not wanted and 
may spoil alcoholic beverages, or the conversion of alcohol to 
vinegar may be accompanied by the production of volatile sub- 
stances with a suffocating odor. There is no clearer evidence of 
the revolution introduced by Pasteur in the biochemical sciences 
than to compare the approach to the study and control of these 
"diseases of fermentations" before and after his work. Before him, 
the appearance of undesirable products was assumed to be the 
result of faulty chemical reactions. Liebig regarded the diseases 
of wine as due to the changes that wine was constantly under- 
going. Under optimum conditions, he taught, the wine reached 
the end of fermentation in such a state that its sugar and the 
organic matter serving as ferment were equally exhausted. If 
there had been too little ferment in the beginning, a portion of 
the sugar remained unchanged, and the wine was sweet, that is 
to say, incomplete. If there had been too little sugar, on the con- 
trary, some ferment remained which continued to work and to 
produce vitiations of the flavor. This explanation was universally 
accepted, and paraphrased in all textbooks. 

Pasteur, being convinced that each type of fermentation is 


caused by a specific microorganism, contributed to the problem 
two Independent concepts which, found immediate application 
in practical technology. He recognized that bad fermentations are 
commonly due to contaminating microorganisms which generate 
undesirable products. He also emphasized that the activities of a 
given microorganism are conditioned by the physicochemical 
conditions of its environment and that in consequence undesir- 
able products may be formed even by the right organism if the 
conditions of fermentation are not adequately controlled. Thus, 
in vinegar making., the oxidation of alcohol by Mycoderma aceti 
may either fall short or go beyond the ideal point If the oxy- 
gen supply is not adequate, incomplete oxidation gives rise to 
aldehydes, intermediate between alcohol and acetic acid, that 
impart to the product a suffocating odor. The Mycodenna lives 
with difficulty under these conditions and may even die. Under 
other conditions, it may carry the oxidation too far and ruin the 
vinegar by converting the acetic acid into water and carbonic 
acid; this is likely to happen when all the alcohol in the nutrient 
fluid has been exhausted. These examples show that the chemical 
performance of microorganisms is conditioned by the nutritional 
and respiratory conditions under which they live, and Pasteur 
did not miss the occasion to suggest that his observations on the 
biochemical behavior of Mycodenna might have a bearing on 
the disturbances of oxidations that occur in animal tissues. 

The possibility that unfavorable environmental conditions may 
cause physiological disturbances in other microbiological proc- 
esses was always present in Pasteur's mind, and recurs in casual 
remarks scattered throughout his writings. Had not circumstances 
led him to become involved in those diseases either of fer- 
mentations or of animals and man which are brought about by 
foreign microorganisms, he could certainly have traveled with 
success the road to the modern concepts of physiological and 
metabolic diseases. 

A statement left by M. Bigo's son clearly shows that Pasteur 
soon learned to correlate many of the difficulties in the fermen- 
tation process with the presence of abnormal formed elements 


mixed with the yeast globules in the fermenting fluids. "He had 
noticed by microscopic examinations that the globules were 
round when fermentation was healthy, that they lengthened when 
alteration began, and were quite long when fermentation became 
lactic. This very simple method allowed us to watch the process 
and to avoid the fermentation failures which were then so com- 
mon.** While on vacation at Arbois, in September 1858, Pastern- 
had occasion to submit some spoiled Jura wines to microscopic 
examination and saw in them a microorganism presenting mor- 
phological similarity with the lactic acid organism which he had 
just discovered. This observation, and Ms experience in the Lille 
distillery, probably helped him to conclude that the diseases of 
fermentations were caused by foreign organisms which competed 
with, yeast in the fermenting fluid. His studies on the production 
of acetic acid provided further evidence for this view. Souring is 
one of the most common types of deterioration affecting wine; 
and there was no difficulty in tracing it to an oxidation of alco- 
hol to acetic acid similar to that carried out by Mycoderma aceti 
during the making of wine vinegar. In addition to souring, there 
are many other types of alterations that affect unfavorably the 
quality of wines; the Bordeaux wines "turn/ 7 the Burgundy wines 
become "bitter," the Champagnes become "ropy." Fortunately, 
Pasteur was well placed to test by experimentation his general 
thesis that these diseases were also due to contamination by for- 
eign organisms, for some of his childhood friends owned well- 
stocked cellars at Arbois. There, in an improvised laboratory, he 
submitted to systematic microscopic examination all the healthy 
and diseased wines that were submitted to him. From the very 
beginning success rewarded his efforts, and whenever a sample 
was brought defective in some respect, he discovered, mingled 
with the yeast cells, other distinct microscopic forms. So skillful 
did he become in the detection of these various germs that he 
soon was able to predict the particular flavor of a wine from an 
examination of the sediment. In "healthy" wines, the foreign forms 
were absent and yeast cells alone were to be seen. 
Although many bacterial species found in spoiled wines were 


described by Pasteur, he did not investigate the problem with the 
completeness that characterized Ms researches on the produc- 
tion of acetic acid. The chemical changes taking place during 
the production of wine are more complex than are those in- 
volved in vinegar manufacture, and are not completely under- 
stood even today. To Pasteur, however, is due the credit for 
establishing that many diseases of wine are dependent on the 
activity of foreign organisms, a conclusion which was soon found 
applicable to the alterations of other beverages and foodstuffs. 
In addition to Mycoderma aceti, which converts alcohol into 
acetic acid, there is often present in the casks used in the Orleans 
process another microscopic organism, called Mycoderma vini, 
which prevents the formation of vinegar by converting the alco- 
hol into carbon dioxide and water. The casks may also contain 
minute worms, "vinegar worms," which spread over the surface 
of the mixture and prevent Mycoderma aceti from obtaining the 
oxygen required for the conversion of alcohol to acetic acid, 
Pasteur showed that mild heating was sufficient to kill the "vine- 
gar worms" and that by seeding the wine-vinegar mixture with 
large amounts of a pure pellicle of the mother of vinegar, it was 
possible to overcome the undesirable competitors and establish 
Mycoderma aceti over the whole surface. 

Like wine and vinegar, beer was then likely to undergo spon- 
taneous alterations, to become acid, and even putrid, especially 
during the summer. Pasteur demonstrated that these alterations 
were always caused by microscopic organisms, and he described 
his findings in a book published in 1877 under the title Etudes 
sur la biere, ses maladies, causes qui les provoquent. Precedes 
pour la rendre inalterable, avec une theorie nouvelle de la fer- 
mentation? It is entertaining to compare the wealth of loving 
detail covered in the studies on wine with the austerity of the 
discussions in the book on beer. Little is said of brewing in this 

3 A translation of this book was made with the author's sanction under the 
title Studies on Fermentation: the Diseases of Beer, their Causes, and the 
Means of Preventing Them. (London, Macmillan, 1879.) 


book. The middle section has no immediate bearing on beer 01 
on its making. It deals with the mechanism of alcoholic fermen- 
tation, the origin, distribution and transformation of micro- 
organisms all theoretical problems preoccupying Pasteur's mind 
at this stage of his Me. The first chapter shows that the diseases 
of beer are always due to the development of microscopic or- 
ganisms foreign to a good fermentation, and the last chapter 
tells how to prevent their occurrences. In other words, the brew- 
ers were told how to keep beer from becoming bad, not how 
to make it good. The reason was simple: Pasteur did not like 
beer. He had undertaken a study of the brewing industry after 
the war of 1870 merely to produce a biere de la revanche which 
would compete with the German product Duclaux reports that 
Pasteur was amazed to see his friend Berlin recognize between 
different brands subtle shades of taste that were unnoticeable to 
him. Nevertheless, he did succeed in developing practical tech- 
niques for the control of beer diseases. 4 

Following his first observations in French breweries, Pasteur 
decided to visit one of the famous London establishments to con- 
firm his findings and spread his gospel further. The account which 
he has left of his visit to the Whitbread brewery in London re- 
veals the strength of his convictions, and the courage with which 
he submitted them to practical tests. 

"In September, 1871, I was allowed to visit one of the large 
London breweries. As no one there was familiar with the micro- 
scopic study of yeast, I asked to perform it in the presence of 
the managers. My first test dealt with some porter yeast, obtained 
from the outflow of the fermentation vats. One of the disease 
microorganisms was found to be very abundant in it. ... I con- 
cluded therefore that the porter was probably unsatisfactory, and 
in fact I was told that it had been necessary to obtain that very 

4 Pasteur's contribution to the understanding of fermentation processes 
were so important in placing the brewing industry on a rational basis that 
they stimulated the Danish brewer Jacobsen to organize in the Carlsberg 
brewery a research laboratory devoted to the scientific aspects of fermenta- 
tion. The Carlsberg Laboratory soon became one of tie greatest world 
centers of biochemical research. 


same day a new sample of yeast from another London brewery. 
I examined the latter under the microscope and found it purer 
than the old sample. 

"I then asked to study the yeasts of other beers In course of 
fermentation, in particular of ale and pale ale. Here is the draw- 
ing which I made then. One recognizes again the filaments of 
spoiled beer. It was of interest to study the beers which had 
been produced just before the ones of which I had examined the 

"I was given two kinds, both in casks. . . . One was slightly 
cloudy; on examining a drop of it, I immediately recognized three 
or four disease filaments in the microscopic field. The other was 
almost clear but not brilliant; it contained approximately one fila- 
ment per field. These findings made me bold enough to state in 
the presence of the master brewer, who had been called in, that 
these beers would rapidly spoil . . . and that they must already 
be somewhat defective in taste, on which point every one agreed 
although after long hesitation. I attributed this hesitation to the 
natural reserve of a manufacturer whom one compels to declare 
that his merchandise is not beyond reproach. . . . 

TThe English brewers . . . confessed that they had in their 
establishment a large batch of beer that had completely spoiled 
in the casks in less than two weeks. ... I examined a sample of 
it under the microscope without at first detecting the disease or- 
ganisms; however, presuming that the beer had become clear as 
a result of being kept still, and that the disease organisms had 
become inert and settled in the bottom of the casks, I examined 
the deposit which turned out to consist exclusively of the dis- 
ease organisms, without even being mixed with the alcoholic 
yeast. . . . 

*When I returned to the same brewery less than a week later, 
I learned that the managers had made haste to acquire a micro- 
scope and to change all the yeasts which were in operation at the 
time of my first visit.** 

Time and time again, Pasteur reiterated his views concerning 
the origin of the alterations of fermenting fluids, and he sum- 


marized in the following terse statements how his investigations 
had led him to a practical solution of the problem. 

"We have shown that the changes that occur in the beer yeast, 
in the worts and in the beer itself, are due to the presence of 
microscopic organisms of a nature totally different from those 
belonging to the yeast proper. These organisms, by the products 
resulting from their multiplication in the wort, in the beer yeast, 
and in the beer, alter the properties of the latter and militate 
against its preservation. 

"We have further demonstrated that the organisms responsible 
for such alterations, these disease ferments, do not appear spon- 
taneously, but that whenever they are present in the wort or in 
the beer it is because they have been brought from without, 
either by dust in the air, or by the vessels, or by the raw materials 
which the brewer employs. 

"We also know that these disease ferments perish in malt wort 
raised to the temperature of boiling, and, as a necessary conse- 
quence of this fact, we have seen that malt wort exposed to pure 
(sterile) air does not undergo any sort of fermentation after hav- 
ing been boiled. 

"As all the disease germs of wort and beer are destroyed in 
the copper vessels in which the wort is heated, and as the intro- 
duction of pure yeast from a pure beer cannot introduce into 
the latter any foreign ferment of a detrimental nature, it follows 
that it ought to be possible to prepare beers incapable of de- 
veloping any mischievious foreign ferments whatever. This can 
be done provided that the wort coming from the copper vessels 
is protected from ordinary air . . , and fermented with pure 
yeast, and that the beer is placed in vessels carefully freed from 
ferments at the end of the fermentation." 

As microorganisms can spoil wine, vinegar and beer, it is essen- 
tial to avoid introducing them during and after the manufacturing 
process, or to prevent their multiplication, or to kill them after 
they have been introduced. The introduction of foreign micro- 
organisms in the finished product can be minimized by an Intel- 


ligent and rigorous control of the technological operations, but 
cannot be prevented completely. The problem therefore is to 
inhibit the further development of these organisms after they 
have been introduced into the fermented fluid. To this end, Pas- 
teur first tried to add a variety of antiseptics, especially hypo- 
phosphites and bisulites which are without too objectionable 
an odor and a taste in dilute solutions, and which are converted 
to nontoxic sulfates or phosphates by oxidation. However, the 
results were mediocre or negative and, after much hesita- 
tion, he considered the possibility of using heat as a sterilizing 

There was much to be feared from the damaging effect of 
heat on fermented fluids, especially on wine, for one does not 
need to be a connoisseur to realize that "cooked wine" is no 
longer real wine. Fortunately, Pasteur's knowledge of the sus- 
ceptibility of microorganisms to teat suggested to him that the 
problem was not as hopeless as appeared at first sight. He knew 
that wine is always slightly acidic and that heat is a much more 
effective disinfectant under acid than under neutral conditions; 
indeed, a temperature as low as 55 C. proved sufficient to im- 
prove the keeping qualities of ordinary wine. On the basis of his 
prior investigations of the effect of air on the aging of wine, Pas- 
teur further postulated that heat might not have any significantly 
deleterious effect on the bouquet of wine if applied only after 
the oxygen originally present in the bottle had become exhausted, 
and this presumption proved true. These considerations led to 
the process of partial sterilization, which soon became known 
the world over under the name of "pasteurization/* and which 
was found applicable to wine, beer, cider, vinegar, milk and 
countless other perishable beverages, foods and organic products. 

It was characteristic of Pasteur that he did not remain satisfied 
with formulating the theoretical basis of the process of heat 
sterilization, but took an active interest in designing industrial 
equipment adapted to the heating of fluids in large volumes and 
at low cost. His treatises on vinegar, wine and beer are illus- 
trated with drawings and photographs of this type of equip- 


ment, and describe in detail the operations involved in the process. 
The word "pasteurization* is, indeed, a symbol of his scientific 
life; it recalls the part he played in establishing the theoretical 
basis of the germ theory, and the phenomenal effort that he de- 
voted to making it useful to his fellow men. It reminds us also 
of his oft-repeated statement: "There are no such things as pure 
and applied science there are only science, and the applications 
of science." 

The pasteurization process was soon attacked from many dif- 
ferent angles. First to be overcome was the natural hesitation of 
those who feared that heating would spoil the qualities of fine 
wines. With the organizing genius that he exhibited so many 
times, Pasteur established an experimental cellar in which sam- 
ples of heated and unheated wines of different origins and quali- 
ties were kept for periods of several years. At regular intervals 
of time, an official commission of winetasters compared the 
products and published reports, which were uniformly favorable 
to pasteurization. He also arranged to have heated and unheated 
wines used in comparison on ships of the French Navy during 
long sea voyages, and thus obtained additional confirmation of 
the superiority of the pasteurized products. He published in 
agricultural journals practical descriptions of his process and its 
merits. To carry still more conviction, he reported in dialogue 
form (as reported on pages 71 and 72) the visit received from the 
Mayor of Volnay who had come to him an unbeliever and had 
left converted. He even quoted with pride that his process was 
used with success in faraway California: 

"Across continents and oceans, I extend my most sincere thanks 
to this honest wine maker from California whose name I am 
sorry not to know. 

"It is inspiring to hear from the citizen of a country where 
the grapevine did not exist twenty years ago, that, to credit a 
French discovery, he has experimented at one stroke on 100,000 
liters of wine. These men go forward with giant steps, while we 
timidly place one foot in front of the other, often more inclined 
to disparage than to honor a good deed/* 


Wliile Pasteur tad to straggle to establish the practicability and 
safety of partial sterilization by heat, at the same time the ac- 
cusation was leveled against him that the process was not new: 
that Appert, in particular, had shown that wines could be warmed 
without altering their taste. As soon as he learned of these old 
experiments, he acknowledged their importance, but pointed out 
that there were theoretical and practical differences between 
Apperf s method and his own. Having also been told that the 
heating of wine had been practiced for a long time at Meze in 
the South of France, he hastened there to investigate the matter. 
After verifying the fact, he made clear that his process differed 
markedly also from the one practiced at Meze. "They do heat 
the wine at Meze, but it is to age it more speedily. For this pur- 
pose, they warm it in contact with the air, for a long time, so 
as to bring about changes in taste, which sometimes exceed the 
limit, and which it is then necessary to correct These gropings 
about in the dark show that the wine merchants of Meze do not 
have any clear idea of what they are about, and have not read 
my book. It would be to their interest to do so, for I give the 
theory of their practice. Moreover, what does this long and 
dangerous warming in contact with the air have in common with 
the rapid heating to 50 C. ? protected from the air, that I recom- 

There were other claims of priority which led to bitter public 
controversies. Pasteur should have been wise enough to trust to 
the judgment of time, but profound faith is always a little in- 
tolerant, and such faith was his. These polemics are of no 
interest today, except as they reveal the fundamental weakness 
of empirical practices in comparison with those based on rational 
theory. The heating of wine had been practiced sporadically 
from all antiquity, and some vintners knew that it could be done 
under certain conditions without spoiling the flavor of the 
product. But it was Pasteur who first provided a rational basis 
for the empirical procedure, by establishing that certain altera- 
tions were caused by contaminating microorganisms, and that 
these organisms could be inhibited by heat. His theoretical studies 


led to standardized and dependable techniques for the preserva- 
tion ? not only of wine, but also of other perishable fluids. 

The general body of knowledge and of techniques on which 
the germ theory of fermentation was based had long been avail- 
able, and the only surprising thing is that the scientific world had 
refused to accept the obvious interpretation of the known facts. 
Intent on their mission to prove that all physiological phenomena 
could be interpreted in terms of physicochemical reactions, the 
opponents of the theory did not wish to consider life in the proc- 
esses which they studied, and consequently they failed to recog- 
nize it in the form of yeast or of other ferments. For a similar 
reason, Pasteur had failed a few years earlier to recognize in 
synthetic malic acid a mixture analogous to the one that he him- 
self had separated into left and right components, because he 
did not believe that optically active compounds could be syn- 
thesized from inactive precursors in the laboratory. The mind 
can be a piercing searchlight which reveals many of the hidden 
mysteries of the world, but unfortunately, it often causes such a 
glare that it prevents the eyes from seeing the natural objects 
which should serve as guideposts in following the ways of 

Much perspicacity, intellectual courage, and forcefulness were 
needed to overpower the formidable physicochemical philosophy 
of the time. In fact, it is to this day a source of wonder that Pas- 
teur, then still a young man known to but a few chemists, dared 
to challenge Liebig on his own ground, and managed within a 
few years to impose the vitalistic theory of fermentation upon 
the scientific and lay public. That he dared is evidence of his 
fighting temperament and of his faith in the correctness of his 
intuitive judgment, for he had no proof of the living nature of 
yeast when he took his stand on the side of Cagniard de la Tour, 
Schwann, Ziitzing and Turpin. That he succeeded so rapidly 
was due to his skill as an experimenter and to the vigor of his 
fighting campaign. 

As will be recalled, all of his former training and research expe- 



rience had been in the fields of physical and organic chemistry. 
And yet, within a few weeks after his Brst contact with the fer- 
mentation problem, we find him borrowing the experimental ap- 
proach and the techniques of the biologist, using the microscope 
not only to investigate chemical substances, but even more to 
unravel the nature of the agents involved in the fermentation 
processes. Just as the study of fermentation and putrefaction was 
then considered the province of the chemist, so knowledge of 
microbial life was the specialty of a few botanists interested in 
the description of the microscopic forms as biological curiosities, 
with at best only a vague awareness of their chemical activities. 
It was therefore an extraordinary intellectual feat that Pasteur 
should have been able to adopt immediately the biological point 
of view without being inhibited by the fear and inertia that inves- 
tigators have to overcome in passing from one laboratory disci- 
pline to another. The intellectual vigor required by this attitude 
may not be obvious to the modern man who, through education 
and publicity, has been made almost hyperconscious of the ubiq- 
uitous presence of living germs in the world around him, and of 
their role as agents of fermentation, putrefaction, rotting and 
disease. In 1857, however, the chemist who adopted the vitalistic 
theory of fermentation had to face the same odds that would 
today confront a telephone engineer interested in developing the 
use of telepathy for the transmission of thought. 

As soon as Pasteur became convinced that living microorgan- 
isms were the primary cause of fermentation and putrefaction, 
he devised means for recognizing and studying them and showed 
that one could control their activities almost at will. Thus, count- 
less experiments and improved industrial practices emerged as the 
fruits of the germ theory, whereas Liebig's theory had no opera- 
tional value whatever. Even when dignified with the name of 
"catalytic theory" by Berzelius, the view that organic substances 
in decomposition imparted to the sugar molecules an agitation 
which converted them into alcohol, or lactic acid, or butyric acid 
did not lead to any new experiment and was of no help in the 
technology of fermentation. In fact, the contrast between the 


bareness of the chemical theory and the wealth of theoretical and 
practical consequences which were derived from the germ theory 
assured the rapid growth of the latter as soon as it found in Pas- 
teur a determined leader. 

It has been said that Berzelius's and Liebig's theories came 
closer than did the vitalistic theory to the ultimate understanding 
o fermentation phenomena. Indeed, in 1897, as will be recounted 
later, Biichner succeeded in extracting from yeast a lifeless juice 
capable of converting sugar into alcohol. Berzelius's catalytic 
theory turned out to be fundamentally correct, and Biichner's 
yeast juice was one step nearer the ultimate cause of fermenta- 
tion than was Pasteur's living yeast. It is also true, however, that 
in 1860 no progress could be made in the understanding of fer- 
mentation until the chemical activities of microorganisms had 
been recognized and until techniques had been worked out for 
the study and control of microbial life. In their activities, further- 
more, men are not governed by concern with ultimate truths, but 
rather by practical common sense. Liebig could argue that to in- 
voke vitalism was to take a backward step; his contemporaries 
believed Pasteur, because the emphasis on the living nature of 
yeast and ferments was productive of useful results. Men may 
propound many kinds of philosophies in their discourse, but in 
general, they act pragmatically. Throughout his life, Pasteur was 
amazingly pragmatic in his operations; for him, a theory was 
right which was useful in action. In 1860, the germ theory was 
more useful than the chemical theory because it was better 
adapted to the discovery of new scientific facts and to the im- 
provement of industrial practices. 

There is something pathetic in Liebig's last attempts at defend- 
ing his views against those of Pasteur. After so many years, he 
had not been able to contribute one positive finding to substan- 
tiate the mechanism of fermentation that he advocated. In his 
long memoir of 1869, he could report only his inability to obtain 
fermentation and multiplication of yeast in a synthetic medium 
free of organic nitrogen. It is probable that his failure came from 
the fact that he attempted to repeat Pasteur's experiment with a 


strain of brewer's yeast having such exacting nutritional require- 
ments that the microorganisms were not satisfied with the syn- 
thetic media then available. As he did not believe in the possibil- 
ity of growing yeast in the absence of albuminoid matter, Liebig 
did not make the effort required to solve the technical problems 
which would have permitted him to duplicate Pasteur's results. 
He also stated in the same memoir that the bacterium, Myco- 
derma aceti, which Pasteur claimed to be responsible for the 
production of acetic acid, was not present in the German vinegar 
works; for, he said, "on wood shavings which had been used for 
twenty-five years in a large vinegar factory in Munich, there was 
no visible trace of Mycoderma, even when observed under the 
microscope/' Liebig was wrong; he failed to see the Mycoderma 
because he did not want to see them. This great man, whose 
vision, learning and energy had founded the science of biochem- 
istry, presents with particular acuity the tragic spectacle of a 
brilliant mind become slave of preconceived ideas and blinded 
by them. 

Pasteur replied to Liebig's memoir by a short note in which he 
scorned to carry on the argument but instead went straight to 
the facts. Liebig had questioned the validity of two of his claims. 
Pasteur challenged him to submit the matter to a commission of 
scientists before whom these facts would be put to an objective 
test. He offered to prepare, in an exclusively mineral medium, as 
much yeast as Liebig could reasonably demand, and to demon- 
strate the presence of the Mycoderma aceti on all the beech 
shavings of the Munich vinegar factory. He also suggested that 
the Munich manufacturer bring to boiling temperature the vats 
containing the wood shavings and then reintroduce alcohol into 
them. Under these conditions, he affirmed, no vinegar would be 
produced because the bacteria would have been killed by heat- 
ing. Liebig ignored the challenge, and never replied, either be- 
cause he was convinced, or, more likely, because he was over- 
powered by the greater vigor of his opponent The germ theory 
of fermentation immediately gained widespread acceptance. 
Microbiology, which heretofore had been the odd occupation of 


a few botanists, became within a few years one of the most rapidly 
growing sections of biological sciences. A new haunt of life had 
been discovered and Its exploration and exploitation gave rise to 
one of the boom periods of biology. 

The theory states that, in a krge measure, the transformations 
of organic matter are carried out through the agency of micro- 
organisms. For each type of transformation, there exists one or 
several types of organisms specialized in the performance of the 
chemical reactions involved in this transformation. Each micro- 
bial type is characterized not only by its behavior as a chemical 
agent, but also by the fact that it demands highly selective con- 
ditions for optimum growth and activity. By taking advantage of 
this selectivity in requirements, man can become master of mi- 
crobial life, favoring one form by providing conditions that are 
optimum for its multiplication and activities, repressing others 
by creating an environment unfavorable to them. He can even 
modify somewhat the chemical reactions which accompany 
microbial life by modifying the conditions under which micro- 
organisms grow and carry on their chemical activities. Thus, fer- 
mentation and putrefaction are no longer vague and uncontrol- 
lable transformations, indeterminate in their cause and origin, 
taking place in haphazard manner under the influence of ill- 
defined organic matter; they are predictable phenomena due to 
the existence and activity of specific microbial agents that can 
be domesticated to function according to the needs and wishes 
of man, Such was the central theme that Pasteur was to develop 
during the rest of his scientific career. With him began the 
domestication of microbial life. 


Spontaneous Generation and the Role of 

Germs In the Economy of Nature 

Omne mvum ex vivo. 


Why then, asked the Sirian, do you quote this Aris- 
totle in Greek? 

It is, the learned man replied, because it is wiser to 
quote that which one does not understand at all, in 
the language that one comprehends least 


IT is common observation that all dead plants and animals un- 
dergo decomposition, again to become part of the envelope of 
soil, water and atmosphere at the surface of the earth. Should 
any component of organic life remain undestroyed and be al- 
lowed to accumulate, it would soon cover the world, and imprison 
in its inert mass the chemical elements essential to the continuity 
of life. Of this, however, there is no danger. Substances of animal 
or plant origin never accumulate in nature, for any organic prod- 
uct which finds its way into soil or water undergoes, sooner or 
later, a chain of alterations which break it down stepwise, into 
simpler and simpler compounds water, carbon dioxide, hydro- 
gen, ammonia, elementary nitrogen, mineral salts. It is in this 
fashion that after death the chemical elements are returned to 
nature for the support of new life. "All are of the dust, and all 
turn to dust again.** 

The eternal movement from life, through organic matter, and 
back into life, has inspired the psalms and songs of poets, and 
scientists have long known that it is essential to the maintenance 


of life on the surface of the earth. Before the microbiological era, 
however, the cycle of organic matter was surrounded with mys- 
tery, as appears from a note found after Lavoisier's death among 
his unpublished manuscripts. "Plants extract from the air that 
surrounds them, from water and In general from the mineral 
kingdom, all the substances necessary to their organization. 

"Animals feed either on plants or on other animals which them- 
selves have fed on plants, so that the substances of which they are 
constituted originate. In final analysis, from air or from the min- 
eral kingdom. 

"Finally fermentation, putrefaction and combustion endlessly 
return to the atmosphere and to the mineral kingdom the prin- 
ciples which plants and animals had borrowed from them. What 
is the mechanism through which Nature brings about this marvel- 
ous circulation of matter between the three kingdoms?" 

During the first six decades of the nineteenth century, chemists 
had described with ever-increasing detail the chemical transfor- 
mations by which the chemical constituents derived from the air 
and from the mineral kingdom become the substances of which 
plants and animals are made; but the mechanism through which 
organized matter was returned to nature after death was as little 
understood in 1860 as in Lavoisier's time. 

However, once the demonstration had been made that fermenta- 
tion and putrefaction were caused by living microorganisms, it be- 
came apparent that many of the other transformations of organic 
matter might also result from the activities of microbial life. 
Pasteur saw immediately the large implications of the new point 
of view, and presented his interpretation of Lavoisier's theme in 
a letter written to the Minister of Public Education in April 1862. 
The vision of a cosmic cycle of organic matter, eternally carried 
out by infinitely small microorganisms, appeared to him with 
dramatic quality. What Lavoisier had said in a few words, in the 
disciplined language of the Enlightenment, Pasteur elaborated 
with the vehemence of the prophets. Even in science, the re- 
dundance of the romantic period had replaced the classic re- 


We know that the substances extracted from plants fer- 
ment when they are abandoned to themselves, and dis- 
appear little by little in contact with the air. We know that 
the cadavers of animals undergo putrefaction and that soon 
only their skeletons remain. TMs destruction of dead organic 
matter is one of the necessities of the perpetuation of life. 

If the remnants of dead plants and animals were not de- 
stroyed, the surface of the earth would soon be encumbered 
with organic matter, and life would become impossible be- 
cause the cycle of transformation . . . could no longer be 

It is necessary that the fibrin of our muscles, the albumin 
of our blood, the gelatin of our bones, the urea of our urines, 
the ligneous matter of plants, the sugar of their fruits, the 
starch of their seeds ... be slowly resolved to the state of 
water, ammonia and carbon dioxide so that the elementary 
principles of these complex organic substances be taken up 
again by plants, elaborated anew, to serve as food for new 
living beings similar to those that gave birth to them, and so 
on ad infinitum to the end of the centuries. 

Pasteur outlined in the same letter his creed concerning the all- 
important role played by microbial agents in the economy of 
nature and in the causation of disease. Without denying that 
ordinary chemical forces may slowly attack organic matter, he 
affirmed that decomposition was chiefly caused by "microscopic 
living beings, endowed with special properties for the dissociation 
of complex organic substances, or for their slow combustion with 
fixation of oxygen." Thus, he pointed out, 'When the sweet juice 
of a plant or a fruit is abandoned to itself, air brings to it yeast 
which transforms the sugar into alcohol and carbon dioxide; then 
other microbial agents intervene which oxidize the alcohol to 
acetic acid, and still others which complete the process of oxida- 
tion to carbon dioxide, thereby returning practically all of the 
carbon originally present in the sugar back to the atmosphere 
where it becomes once more available for the growth of plants. 
It is by interrupting the oxidation of sugar either at tie alcohol 
or at the acetic acid level that man has established empirically the 
industries which give him wine, beer, or vinegar . . . And thus 


It becomes obvious . . . how pure science . . . cannot advance 
one step without giving rise, sooner or later, to industrial appli- 
cations/* Pasteur also saw clearly that "the study of germs offers 
so many connections with the diseases of animals and plants, 
that it certainly constitutes a first step in the ... serious in- 
vestigation of putrid and contagious diseases," and announced in 
these words the program to which he was to devote the remainder 
of his scientific life: "To pursue, by rigorous experimentation, the 
study of what is, in my opinion, the immense physiological role 
of the infinitely small in the general economy of nature/* 

One fundamental question had to be answered before "rigor- 
ous experimentation'* in this field became possible. Where did 
these ^infinitely small" come from? Did they originate from par- 
ents identical to themselves? Or did they arise de novo whenever 
conditions were favorable for their existence? Thus Pasteur was 
compelled to consider the problem of the origin of microbial life 
and to become involved in the controversy on spontaneous gen- 

Under a thousand symbols, men of all religions and philoso- 
phies have sung and portrayed the repeated emergence of life 
from inanimate matter. There is a poetic fascination in the ancient 
creed that life is always arising anew from matter, as Aphrodite 
came out of the foam of the sea. Men have also long believed, and 
indeed many still believe, that vitality is an indestructible prop- 
erty; that all living things are composed of organic parts, in 
themselves eternal, and capable of entering into the most diverse 
compositions to recreate life. Spontaneous generation, according 
to a view which was still prevalent in the nineteenth century, was 
the recombination of some of these eternal fundamental units of 
life set free by the prior death of another living thing. 

Throughout the ancient civilizations, the Middle Ages and the 
Renaissance, it was widely believed that plants and animals 
could be generated de novo under certain peculiar circumstances; 
that eels arose without parents from the ooze of rivers and bees 
from the entrails of dead bulls. Weird formula for the creation of 


life found their way into learned textbooks, and as late as the six- 
teenth century the celebrated physiologist van Helmont affirmed 
that one could create mice at will by putting in a container some 
dirty linen together with a few grains of wheat or a piece of 

Slowly, men ceased to believe in the spontaneous generation 
of grubs, maggots, tapeworms and mice but it remained the gen- 
eral opinion that the microbial life which crowds fermenting and 
putrefying fluids is a product of the alteration of organic mate- 
rials and results from some form of spontaneous generation. And, 
indeed, it was often observed that countless bacteria made their 
appearance in a flask of broth or milk, previously heated to de- 
stroy living forms, whenever the broth or milk went bad. These 
bacteria were so small and seemed to be so simple in structure 
that they appeared to be at the threshold of life. Was it not pos- 
sible therefore that they came into being out of inanimate organic 
matter? Were they not primitive enough to be excluded from the 
law Omne vivum ex vivo? Experimentation on this problem be- 
gan around 1750 and was pursued over a century. Some experi- 
menters, like the Irish Catholic priest Needham, claimed that 
they could bring about at will the creation of living microscopic 
agents in infusions which had been sterilized by heat, while 
others, following the Abbe Spallanzani, maintained that life could 
never be spontaneously generated from dead matter. Naturalists, 
philosophers and wits kept the debate alive by contributing to it 
observations and experiments, as well as religious and philosophi- 
cal arguments. In the article "God" of the Dictionnwre Philo- 
sophique, the skeptical Voltaire amused himself at the thought 
that Father Needham should claim the ability to create life, while 
atheists, on the other hand, "should deny a Creator and yet at- 
tribute to themselves the power of creating eels." Despite labori- 
ous experimentation and even more strenuous arguments, the 
problem remained without definite conclusion, each of the ad- 
versaries showing clearly that the others were wrong in some de- 
tails, but not succeeding in proving that he himself was right on 
all points. 


It was known that putrescible organic infusions in which life 
had been destroyed by prolonged healing at high temperature 
often remained unspoiled, and that microscopic life usually did 
not develop in them, as long as they were protected from contact 
with air. The mere admission of air, however, was sufficient to 
cause the fluids to enter upon fermentation and putrefaction, and 
to bring about the appearance of a great variety of microorgan- 
isms within a few days. The believers in spontaneous generation 
saw in these changes evidence that oxygen was necessary to in- 
itiate the generation of life. Their adversaries claimed, on the con- 
trary, that air merely introduced into the organic fluids the living 
germs of fermentation and putrefaction. To prove the latter thesis, 
Franz Schiilze in 1836 and Theodor Schwann in 18S7 passed the 
air through caustic potash or concentrated suUFuric acid, or 
heated it to a very high temperature, in order to destroy the hypo- 
thetical living germs before admitting it to the organic fluid. And 
indeed, under these conditions, the fluids often remained un- 
altered, the microscopic agents failed to appear. 

In 1854, and again in 1859 and 1861, an interesting modifica- 
tion of these experiments was introduced by Heinrich Schroder 
and Theodor von Dusch. Instead of heating the air or drawing it 
through sulfuric acid before permitting it to enter the infusion, 
these authors simply filtered it through cotton plugs, as had been 
done a few years earlier by the chemist Loewel. He had found 
that air could be deprived of its ability to induce the crystalliza- 
tion of supersaturated solutions if it passed through a long tube 
filled with cotton wool. Similarly, Schroder and von Dusch found 
that meat boiled in water and continuously receiving fresh air 
filtered through the cotton tube remained unchanged and de- 
void of unpleasant odor and of microbial population for long 
periods of time. 

These observations clearly suggested that the germs of fermen- 
tation and of putrefaction were introduced from the air into the 
organic infusions and did not generate there de novo. Unfortu- 
nately, whatever the precautions used to destroy or exclude these 


germs, the experiments now and then failed, microbial life ap- 
peared, and fermentation and putrefaction set in. These failures 
shook the faith of many, indeed, often of the experimenters them- 
selves. Thus, Schroder and von Dusch had particular difficulty in 
protecting milk and egg yolk from putrefaction and concluded 
that the germs of putrefaction came from the substances them- 
selves and were derived from animal tissues. As mentioned in an 
earlier chapter, even Helmholtz had found it necessary to reach 
a similar conclusion. The possibility that spontaneous generation 
occurred in the case of putrefaction clearly left the door open 
for the possibility of its occurrence in all other microbial ac- 

This confused state of affairs was brought to a crisis in 1858 
when Felix Archimede Pouchet read before the Paris Academy 
of Sciences a paper in which he claimed to have produced spon- 
taneous generation at will by admitting air to the sterilized pu- 
trescible matter under carefully chosen conditions. Pouchet was 
director of the Museum of Natural History in Rouen, and an 
honored member of many learned societies. He was, according 
to Tyndall, "ardent, laborious, learned, full not only of scientific 
but of metaphysical fervour/ 7 and had reached his conviction by 
meditating over the nature of life: "When by meditation, it be- 
came evident to me that spontaneous generation was one of the 
means employed by nature for the reproduction of living things, 
I applied myself to discover the methods by which this takes 
place/' Conviction based on philosophical premises was a danger- 
ous start on the subject of spontaneous generation, which was so 
full of experimental pitfalls. 

Pouchefs experiment consisted in taking a flask of boiling 
water, which he hermetically sealed and then plunged upside 
down into a basin of mercury. When the water had become quite 
cold, he opened the flask under mercury and introduced half a 
liter of oxygen, and also a small quantity of hay infusion previ- 
ously exposed for a long time to a very high temperature. These 
precautions, he believed, were adequate to plug every loophole 


against the admission of living organisms into Ms flask, and yet 
microbial growth regularly appeared within a few days in the 
hay infusion. 

The following year, Pouchet presented his views and findings in 
an elaborate work of 700 pages entitled Heterogenie, which he 
regarded as the final demonstration that life could originate 
anew from inanimate solutions. Although criticized by some of 
the leading French physiologists, Pouchet's claims produced a 
great sensation in scientific circles. In the hope of encouraging 
experiments that would dissipate the confusion, the Academy in- 
stituted in 1860 the Alhumpert Prize with the following program: 
"To attempt, by carefully conducted experiments, to throw new 
light on the question of the so-called spontaneous generations." 

As early as 1859, the year of publication of the Origin of 
Species, Pasteur had entered into the thick of the fight over the 
origin of Me. It has been suggested that he immediately took 
sides against those who claimed to have demonstrated sponta- 
neous generation because, as a devout Catholic, he could not 
accept the thought of a new creation of life. This interpretation 
is certainly unwarranted. A few years before, Pasteur himself had 
attempted to create life by the action of asymmetrical physical 
and chemical forces, but his studies on fermentation had more 
recently led him to emphasize the specific nature of the fermenta- 
tive reactions a concept incompatible with the haphazard ap- 
pearance of microorganisms which seemed to be a consequence 
of the doctrine of spontaneous generation. At that time, the speci- 
ficity of living species had already become associated with the 
idea of the continuity of the germ cell, and it would have been 
very astonishing had this relationship failed to operate among 
the "infinitely small/' The idea of specificity, born of the work on 
fermentation, involved the concept of hereditary characters, 
which in turn led to the belief in an ordinary kind of generation. 

Biot and Dumas strongly dissuaded Pasteur from attacking the 
problem of spontaneous generation, as they feared that he would 
lose valuable time on this question, which appeared to them out- 


side the range erf scientific inquiry. Pasteur was convinced, how- 
ever, that the solution of the problem was essential to the suc- 
cessful development of his views on the role of microorganisms in 
the economy of nature. He could not be deterred from joining the 
controversy and singled out Pouchef s momentary triumph as 
the first goal for his attacks. 

Pasteur's experiments on tibe problem of spontaneous genera- 
tion have achieved great and deserved fame; but even more inter- 
esting than their performance is the broad strategy of Ms attack 
on the subject. He immediately acknowledged the possibility that 
in our midst, or somewhere in the Universe, life may still be 
creating itself. This possibility cannot and should not be denied. 
But what can be done is to evaluate the claims of those who pre- 
tend to have seen life emerge anew, or to have brought about 
conditions under which its spontaneous generation is possible. 
To this task, he set himself and devoted an immense amount of 

It was generally agreed that an organic infusion, even though 
subjected to prolonged heating, would always undergo fermenta- 
tion or putrefaction shortly after ordinary air was admitted to it. 
Was this due to the fact that natural air was an essential factor 
for the new emergence of life, as the proponents of spontaneous 
generation claimed, or was it merely that air contained preformed 
and viable germs? This question, suggested to Pasteur countless 
experiments with all types of organic fluids: yeast extract, broth, 
milk, urine, blood and with air heated and filtered under all 
kinds of conditions. He borrowed the techniques and procedures 
developed by his predecessors in the problem, but, by paying 
infinite attention to minute technical details, he finally succeeded 
in arranging tests that always gave the desired result. He ob- 
served, for example, that the mercury used at the time of readmit- 
ting the air into the heated flasks always contained dust and living 
germs on its surface. By eliminating mercury from the experi- 
mental technique, he eliminated at the same time a source of con- 
tamination of the fluids and air. He also recogaized that if milk, 
egg yolk and meat did putrefy even after heating at 100 C., it 


was not, as Helmholtz, Schroder and many others had believed, 
because putrefaction was a process inherent in these nitrogenous 
materials, but only because the germs which they contained had 
to be heated at somewhat higher temperatures to be inactivated. 
This greater resistance was due in part, but not wholly, to the 
fact that germs are less readily destroyed by heat at the neutral 
reaction of milk or egg yollc than at acid reactions. For example, 
a concoction of yeast which is slightly acidic is easily sterilized 
by a short boiling under normal conditions, but needs to be 
heated at 110 C. if neutralized by the addition of sodium car- 
bonate; it then behaves like milk. All organic fluids heated at a 
sufficiently high temperature remained sterile when air sterilized 
by heat or by filtration was admitted to them. As these same 
heated fluids quickly showed living things in the presence of 
ordinary air, it appeared obvious that the germs of life came from 
the air. 

These new experiments, however reproducible, left open the 
possibility that Me demands the presence of a (chemical) "vital 
principle/' present in organic fluids and in natural air, but de- 
stroyed by prolonged heating and by filtration. This objection, 
so intangible and yet difficult to ignore, stimulated great discus- 
sion in the scientific atmosphere of the 1860's and particularly in 
Pasteur's laboratory. Even those of his friends who had advised 
him to keep away from the spontaneous generation controversy 
now took a lively interest in it. The great Jean Baptiste Dumas, 
who had become one of the majestic officials of the Empire, now 
and then came down from his heights to watch the details of the 
scientific debate, and to encourage the Pasteur camp. More in- 
volved in the actual proceedings was Balard, who followed Pas- 
teur's career with as much personal interest as during the crystal- 
lographic period, and whose important contribution to the new 
controversy has been brought to light by Duclaux: "Balard loved 
science. It was sufficient to see him in a laboratory managing a 
piece of apparatus, or carrying out a reaction, to know that he 
was a chemist to his finger tips. But he had a certain natural indo- 
lence, and he was thenceforth satisfied with his share of glory. 






In place of the scientific work that he would have been able to do, 
he preferred that which he found done in the laboratories he 
frequented. . . . There he wished to see all the details, and we 
told him everything, first, because he had an open mind and a 
generous soul, and also because it would have been difficult to 
conceal anything from him: he put into his interrogations at the 
same time so much shrewdness and simplicity! When anyone 
showed him a nice demonstration he admired it with aH his heart! 
And then, one was sometimes rewarded for this confidence: he 
would suggest an idea or reveal a method. ... All the experi- 
ments on spontaneous generation transported Balard with delight, 
and the laboratory became animated with his expansive joy as 
soon as he entered/' 

It was in the course of one of these visits that Balard suggested 
an experimental procedure the use of the swanneck flask 
which was extensively exploited in Pasteur's laboratory to demon- 
strate the possibility of maintaining heated organic infusions in 
the presence of natural air, without causing, thereby, the appear- 
ance of microscopic life. 

After introducing into the flask a fermentable fluid, the experi- 
menter would draw the neck of the flask into the form of a sinu- 
ous S-tube (hence the name "swanneck" flask). The liquid was 
then boiled for a few minutes, the vapor forcing out the air 
through tihe orifice of the neck. On slow cooling, the outside air 
returned to the flask, unheated and unfiltered. As the neck re- 
mained open, the air inside the flask communicated freely with 
the unfiltered and unheated atmosphere outside, and there was 
constant gaseous exchange; yet the fluid in the flask remained 
sterile indefinitely. It was obvious, therefore, that failure of life 
to develop could not be due to any deficiency in the air. That the 
infusion itself was still capable of supporting life could also be 
readily shown, for it was sufficient to allow dust to fall in by 
breaking the neck of die flask to see microscopic life appear, first 
at the spot directly under the opening. 

Why, then, did the flasks remain sterile after air was admitted 
through the swanneck? Why did the germs fail to enter with it? 


It was because the air was washed in the moisture which re- 
mained in the curves of the neck after heating had been inter- 
rupted. In the beginning, when the entrance of the air was rapid, 
the purifying action of this washing was increased by the tem- 
perature of the liquid, still high enough to kill the germs that 
came in contact with it Later, the wet walls of the neck held fast 
the germs of the air as they passed through the opening. In fact, 
when the flask was shaken in such a manner as to introduce into 
the curve of the neck a little drop of the infusion, this drop be- 
came clouded even when the open end had been previously closed 
so that nothing new would enter from the outside. Further, if the 
drop was mixed with the rest of the liquid, the latter became in- 
fected just as if the neck had been broken off. 

Pasteur had already obtained direct evidence that germs of life 
are present in the air by concentrating the fine particles suspended 
in the atmosphere and observing them under the microscope. He 
had aspirated air through a tube in which was inserted a plug of 
guncotton which acted as a filter and intercepted the aerial germs. 
When at the end of the experiment, the guncotton plug was dis- 
solved by placing it in a tube containing a mixture of alcohol and 
ether, the insoluble dust separated from the solvent and settled 
in the bottom of the tube. Under the microscope, the sediment 
was found to contain many small round or oval bodies, indis- 
tinguishable from the spores of minute plants or the eggs of 
animalcules; the number of these bodies varied depending upon 
the nature of the atmosphere and in particular upon the height 
above the ground at which the aspirating apparatus had been 
placed. The dust recovered from the alcohol and ether solution 
always brought about a rapid growth of microorganisms when 
it was introduced into heated organic infusions, despite all pre- 
cautions taken to admit only air sterilized by heat It was thus 
clear that the fine invisible dust floating in the air contained germs 
which could initiate life in heated organic fluids. 

To this evidence, Pouchet and his supporters raised the objec- 
tion that there could not possibly be enough germs in the air to 


account for the generation of life by the techniques used in the 
laboratory. They quoted experiments of Gay-Lussac which 
seemed to show that the smallest bubble of oxygen was sufficient 
to produce putrefaction. If, urged Pouchet, decomposition were 
due to the germs present in a minute bubble, then air would be 
heavily laden with living forms and be "as dense as iron/* 

There were few physiologists who took Pouchef s remarks seri- 
ously, and Pasteur could have afforded to ignore them. This, how- 
ever, was not his bent. By temperament, he could not leave un- 
answered any opposition to what he believed to be the truth. 
Moreover, there were other reasons which made it imperative to 
study the distribution of microorganisms in nature and thus pro- 
vide an answer to Pouchet's objections. Pouchet had gained much 
following among those who welcomed the claim that life could 
be created at will from inanimate matter; thus, the doctrine of 
spontaneous generation, firmly rooted in philosophical convic- 
tions, could derive enough nourishment to survive even without 
strong scientific support. More important, knowledge of the quan- 
titative distribution of microorganisms in the atmosphere was an 
indispensable basis for the development of the germ theory, and 
Pasteur realized that Pouchef s objection could best be answered 
by gaining more accurate information concerning the presence of 
microorganisms in the atmosphere. In fact, the results of filtration 
of air through guncotton had already suggested that great differ- 
ences existed between the number and type of germs in the at- 
mosphere of different localities. 

It was while attempting to answer Pouchet's objections that 
Pasteur carried out some of his most famous experiments of the 
spontaneous generation controversy, experiments which estab- 
lished that the germs of putrefaction and fermentation are quite 
unevenly distributed. The necks of a number of flasks containing 
yeast extract and sugar were drawn out in the flame to a fine 
opening, so that they could be easily sealed when desired. The 
liquid was then boiled to destroy living things and to drive out 
the air, which was displaced by the current of water vapor. The 
flasks, sealed by melting the glass with a blowpipe while the steam 


was escaping, were thus practically empty of air and their con- 
tent remained sterile as long as they were kept sealed. Pasteur 
took these flasks to the places where he wished to make a study 
of the air, and broke the necks with a long pair of pincers. This 
was done with the most exacting precaution, the necks and the 
pincers being passed through the flame of an alcohol lamp in 
order to kill all the germs deposited on them, and the flasks being 
kept throughout the operation as high as possible above his head 
in order to avoid contamination of the air by the dust from his 
clothing. When the necks were broken, there was a hissing sound; 
this was the air entering. The flasks were then resealed in the 
flame and carried to an incubator. 

Even though each flask received at least one third of a liter of 
external air during the operation, there were always some that 
remained sterile, demonstrating that germs do not occur every- 
where. The tests revealed that aerial germs are most abundant in 
low places, especially near cultivated earth. Their numbers are 
smaller in air allowed to remain still for long periods of time 
as in the cellars of the Paris Observatoire and also in the moun- 
tains away from cultivated and inhabited land. Indeed, most of 
the flasks that Pasteur opened in the midst of the Swiss glaciers 
remained sterile, evidence of the cleanness of the atmosphere at 
these high altitudes; a further proof, also, that pure unheated air 
is unable to cause alteration of organic fluids if it does not con- 
tain the living germs of fermentation. 

These experiments produced an enormous sensation in the sci- 
entific and lay public by virtue of their very simplicity, but they 
did not convince the advocates of the theory of spontaneous 

The controversy had now reached beyond the scientific arena 
into that diffuse periphery where religious, philosophical and po- 
litical doctrines were then confusing so many aspects of French 
intellectual life. Pasteur's findings seemed to support the Biblical 
story of Creation, and were in apparent conflict with advanced 
political philosophy. Writers and publicists took sides in the 


polemic, not on the basis of factual evidence, but only under the 
influence of emotional and prejudiced beliefs. Despite Ms indig- 
nation at the war being conducted against him in the scientific 
bodies as well as in the daily press, Pasteur managed to control 
his temper for a few months. It is possible that he could not devise 
at that time any new experimental approach capable of adding 
weight to the evidence already accumulated and, consequently, 
he judged it wiser to wait for a tactical error of his adversaries 
that would expose them to his blows. 

In 1863, Pouchet reported that, in collaboration with two other 
naturalists, Joly and Musset, he had attempted without success 
to duplicate Pasteur's findings concerning the distribution of 
germs in the air. At different altitudes in the Pyrenees, up to the 
edge of the Maladetta glacier at 10,000 feet elevation, the three 
naturalists had collected air in sterile flasks containing heated hay 
infusion. Instead of obtaining tibe results reported by Pasteur, 
they found that "wherever a liter of air was collected and brought 
into contact with an organic fluid, in a flask hermetically sealed, 
the fluid soon revealed the development of living germs." All Pas- 
teur's precautions were said to have been observed, except that the 
necks of the flasks had been cut with a file, and their contents 
shaken before being sealed again. To Pasteur, this absolute con- 
flict with his own results appeared as the long-awaited opening 
for the riposte, a situation where there was no question of theo- 
retical discussion or of philosophical argument. He trusted com- 
pletely in his technique and had no respect for that of his op- 
ponents. To settle the matter, he demanded that a commission be 
appointed by the Academy of Sciences to repeat the experiments 
carried out with such apparently incompatible results by the two 
groups of workers. 

By then, the Academy was on Pasteur's side. In 1862, it had 
granted him the Prix Alhumpert for his Memoire sur les corpuscles 
organises qui existent dans Tatmosphere ... In 1863, the influ- 
ential physiologist Flourens had dismissed the paper of Pouchet, 
Joly and Musset with a terse and scornful statement: "M. Pasteur's 
experiments are decisive. If spontaneous generation is a reality, 


what is needed to bring about the development of animalcules? 
Air and putrescible fluids. Now, M. Pasteur succeeds in putting 
together air and putrescible fluids and nothing happens. Genera- 
tion therefore does not take place. To doubt any longer is to fail 
to understand the question." 

The commission demanded by Pasteur was appointed and 
threw down the gauntlet with the following statement: "It is al- 
ways possible in certain places to take a considerable quantity 
of air that has not been subjected to any physical or chemical 
change, and yet such air is insufficient to produce any alteration 
whatsoever in the most putrescible fluid/* Pouchet and his co- 
workers took the bait. They answered the challenge by declaring 
that the statement was erroneous and they promised to supply 
the proof, adding: "If a single one of our flasks remains unaltered, 
we shall loyally acknowledge our defeat/* Nevertheless, on two 
different occasions and for reasons that need not detain us, they 
refused to agree to the terms of the test organized by the com- 
mission and finally withdrew from the contest. Pasteur, on the 
contrary, arrived with his assistants laden with apparatus and 
ready for the test, which was carried out in ChevreuTs laboratory 
in the Museum of Natural History. He first demonstrated three 
flasks which he had opened on the Montanvert in 1860 and which 
had remained sterile ever since. One was opened and its air 
analyzed, revealing a normal content of 21 per cent of oxygen. 
The second was opened and exhibited countless microorganisms 
within three days. The third flask was left untouched and was 
subsequently exhibited at the Academy of Sciences. Pasteur then 
prepared a new series of sixty flasks before the commission. In 
each was placed a third of a liter of yeast water. The neck was 
narrowed and the fluid boiled for two minutes; fifty-six out of the 
sixty flasks were sealed in the flame. In four the necks were drawn 
out, bent downwards, and left open. Of the fifty-six sealed flasks, 
nineteen were opened in the amphitheater of the Museum of 
Natural History, with the result that fourteen remained sterile 
and five became infected; nineteen were opened on the highest 
part of the dome of the amphitheater and there thirteen of them 


remained sterile. The third set of eighteen flasks was exposed in 
the open air under some poplar trees and only two of them re- 
mained sterile. The four open flasks with swannecks remained 
sterile. A strongly worded official report, published in the Comptes 
Rendw de TAcad&mie des Sciences? recorded Pasteur's triumph 
and, as many then believed, closed the polemic. 

We must, at this point, anticipate by a few years the further 
development of the controversy to point out that, despite the 
spectacular success of Pasteur's experiments in ChevreuTs labo- 
ratory, and also despite the eminence and integrity of the scien- 
tists who witnessed the tests and acted as referees for the Acad- 
emy, the judgment of the commission was based on insufficient 
evidence. Even the most distinguished academicians must bend 
before the superior court of Time, and we know today that they 
were hasty in deciding the issue without more thorough appraisal 
of Pouchef s claims. In reality, both Pasteur and his opponents 
were right as to what they had observed in their respective experi- 
ments, although Pouchet was wrong in his interpretation of the 
findings. But before such a tribunal, nerve as well as right were 
indispensable for securing justice, and Pouchet was overawed by 
the conviction of his opponent. 

The facts are these: Pasteur had used yeast infusion as the 
putrescible material in his experiments, whereas Pouchet had 
used hay infusion. Yeast infusion is easy to sterilize by heat, hay 
infusion excessively difficult. The heat treatment applied by Pas- 
teur would have been insufficient to sterilize the latter. Conse- 
quently the heat applied by Pouchet, which was the same as that 
used by Pasteur, failed to sterilize the hay infusion that he em- 
ployed, thus accounting for the fact that growth usually developed 
in his flasks whereas Pasteur's flasks containing yeast infusion 
remained sterile under the same conditions. 

The want of self-confidence exhibited by Pouchet in this ex- 
traordinary trial, and the judgment in default given by the aca- 
demic tribunal, delayed knowledge of the whole truth by some 
years, for it was not until 1876 that Pasteur's triumph was again 


called into question. There is, perhaps, a moral to be drawn from 
this story. It is the subtle danger that arises from the assumption 
by an official body, however distinguished, of responsibilities be- 
yond its real competence. The authoritative pronouncement of 
the Academy protected Pasteur for a time by throttling renewed 
investigation, especially in France. Fortunately it could not pro- 
tect him from attacks by scientific foes owning no allegiance to 
the august body whose sanction he had so successfully invoked. 
As we shall see, it was to overcome the claims of spontaneous 
generation made in England a decade later, by Bastian, that Pas- 
teur was compelled to recognize the limitations of the experi- 
mental techniques which he had used in his controversy with 
Pouchet, and to establish his claims on a more definite basis. 

By 1864, Pasteur's triumph appeared complete. He had as- 
sembled his results on the origin and distribution of germs in the 
essay, Sur les corpuscules organises qui existent dans T atmosphere. 
Examen de la doctrine des generations spontanees, which was 
published in 1861, and of which Tyndall wrote: "Clearness, 
strength and caution, with consummate experimental skill for 
their minister, were rarely more strikingly displayed than in this 
imperishable essay/' It was indeed, the inauguration of a new 
epoch in bacteriology. 

In 1862, at the age of 40, Pasteur had been elected a member 
of the Paris Academy of Sciences. As his varied scientific activities 
did not particularly fit tim for any of the specialized sections in 
the Academy, he had been nominated in the mineralogical sec- 
tion, on the basis of his early studies in crystallography and also 
of his formal training in chemistry and physics. There is no ques- 
tion, however, that it was the spectacular character of the studies 
on fermentation and spontaneous generation that had placed him 
in the forefront of French science. 

His fame had now reached beyond scientific circles and the 
polemic on spontaneous generation had become one of the lively 
topics of discussion in social gatherings. Although Pasteur himself 
was careful to limit the debate to the factual evidence for or 


against the de novo emergence of life, lie was approved by many 
and blamed by others, as the defender of a religious cause. A 
priest spoke of converting unbelievers through the proved non- 
existence of spontaneous generation, and, on the other side, the 
celebrated novelist, Edmond About, took up Pouchet's cause with 
no better scientific understanding. **M. Pasteur preached at the 
Sorbonne amidst a conceit of applause which must have glad- 
dened the angels.** The lecture to which About referred had been 
an enormous triumph. On April 7, 1864, at one of the "scientific 
evenings" of the Sorbonne, before a brilliant public which counted 
social celebrities in addition to professors and students, Pasteur 
had outlined the history of the controversy, the technical aspects 
of his experiments, their significance and their Imitations. Present- 
ing to his audience the swanneck flasks in which heated infusions 
had remained sterile in contact with natural air, he had formu- 
lated his conclusion in these words of singular beauty: 

"And, therefore, gentlemen, I could point to that liquid and 
say to you, I have taken my drop of water from the immensity of 
creation, and I have taken it full of the elements appropriated to 
the development of inferior beings. And I wait, I watch, I ques- 
tion it! begging it to recommence for me the beautiful spectacle 
of the first creation. But it is dumb, dumb since these experiments 
were begun several years ago; it is dumb because I have kept it 
from the only thing man does not know how to produce: from the 
germs which float in the air, from Life, for Life is a germ and a 
germ is Life. Never will the doctrine of spontaneous generation 
recover from the mortal blow of this simple experiment." 

It has not recovered yet; it may never do so. Today, after al- 
most a century, the fluids in these very same flasks stand unal- 
tered, witness to the fact that man can protect organic matter 
from the destructive action of living forces, but has not yet learned 
the secret of organizing matter into Life. 

But, despite Pasteur's scientific and official triumphs, his op- 
ponents had not been convinced or entirely silenced. In 1864, 
Pouchet brought out a new and larger edition of his book, in 
which he reiterated his belief in spontaneous generation. Here 


and there, other workers also published a few experiments with 
results IB conflict with Pasteur's teachings. It is not essential to 
follow these minor skirmishes as there was to arise in England, 
a few years later, a more formidable challenger to demonstrate 
that the decision of an official academy was not sufficient to ex- 
terminate the hydra of spontaneous generation. In 1872, Henry 
Charlton Bastian published in London an immense tome of 1115 
pages entitled The Beginning of Life; Being Some Account of the 
Nature, Modes of Origin and Transformation of Lower Organ- 
isms, in which the theory of spontaneous generation was again 
reintroduced in its most extreme form. 

Bastian contributed one new fundamental observation to the 
problem. He found that whereas acid urine heated at high tem- 
perature remained clear and apparently sterile when kept from 
contact with ordinary air, it became clouded and swarmed with 
living bacteria within ten hours after being neutralized with a 
little sterile potash. According to Bastian, this established the fact 
that spontaneous generation of life was possible but that Pasteur 
had failed to provide the complex physicochemical conditions 
necessary for its occurrence. Bastian's techniques were crude and 
most of his claims worthless, the results of clumsy experimenta- 
tion, He was correct in stating, however, that urine heated at 
110 C. could still give rise to microbial life following the addition 
of sterile alkali. If they did not arise de novo, where did the germs 
of this life come from? The manner in which this problem was 
solved deserves some consideration, not only because it settled, 
at least for the time being, the problem of spontaneous genera- 
tion, but also because it led Pasteur and his students in France 
and Tyndall in England to work out some of the most useful 
techniques of bacteriological science. 

Bastian had dissolved heated potash in distilled water, unaware 
of the fact that the most limpid water can carry living germs. 
While investigating this problem Pasteur and his assistant Joubert 
recognized that water from deep wells, which had undergone a 
slow filtration in sandy soil, was often essentially or even com- 
pletely free of germs. This observation soon led Chamberland to 


devise the porcelain bacteriological filters now so widely used In 
bacteriological laboratories and formerly as household objects. 

It soon became obvious that there must have been still other 
sources of contamination in Bastian's experiments. During the 
studies on silkworm diseases, which we shall consider in a later 
chapter, Pasteur had become aware of the fact that bacteria can 
exist in dormant phases which are more resistant to heat than 
the active vegetative forms. These resistant forms were exten- 
sively studied by John Tyndall and especially Ferdinand Cohn, 
who named them Tbacterial spores. 9 * Pasteur surmised that the 
samples of urine studied by Bastian were contaminated with a 
few of these bacterial spores which had survived the heating 
process, but were unable to germinate and give rise to visible 
microbial growth until the slight acidity of urine had been neu- 
tralized by the addition of alkali. Fortunately, heating under pres- 
sure at 120 C. was found sufficient to destroy bacterial spores 
and effect thereby complete sterilization of urine and other 
organic fluids. Thus was introduced into bacteriological technique, 
and into many practical operations of public health and tech- 
nology, the use of the autoclave to effect sterilization with super- 
heated steam. It was found on the other hand that although 
120 C. was sufficient for sterilization in the presence of water 
vapor most forms of life were much more resistant to dry heat. 
The discovery of this fact led to the elaboration of many bacterio- 
logical procedures such as the use of ovens reaching 160 C. 
for dry heat sterilization, and the practice of passing test tubes, 
flasks, and pipettes, through the naked flame for the inoculation 
and transfer of microbial cultures. 

While Pasteur and his school were explaining Bastian's results 
and combatting his interpretations, the physicist John Tyndall 
had taken up the torch against spontaneous generation in Eng- 
land. In the course of his studies on the relation of radiant heat to 
gases, Tyndall had been greatly struck by the difficulty of re- 
moving from the atmosphere the invisible particles of dust that 
float in it. This interest in dust led him to drift progressively into 
the discussion on spontaneous generation and to recognize that 


particles carry living organisms. His experiments on the sub- 
ject, published in 1878 1877, provided powerful support for 
Pasteur's views. He presented them again, along with brilliant 
lectures, in Ms book on the Floating Matter of 

the Air in Relation to Putrefaction and Infection, which, when 
published in 1881, played a role almost equal to that of Pasteur's 
writings in accomplishing the final downfall of the doctrine of 
spontaneous generation. 

Tyndall prepared experimental chambers, the interior surfaces 
of which had been coated with glycerine. The closed chambers 
were left untouched for several days until a beam of light passing 
through lateral windows showed that all floating matter of the air 
had settled and become Bxed on the glycerine surfaces. In Tyn- 
dalTs terminology, the air was then **optically empty/' Under these 
conditions, all sorts of sterilized organic fluids, urine, broth, 
vegetable infusions, could be exposed to the air in the chamber 
and yet remain unaltered for months. In other words, optically 
empty air was also sterile air. Thus it became certain that the 
power of the atmosphere to generate bacterial life goes hand in 
hand with its ability to scatter light and therefore with its con- 
tent in dust, and that many of the microscopic particles which 
float in the air consist of microorganisms, or carry them. 

Tyndall, who had been trained as a physicist, displayed like 
Pasteur great biological inventive imagination in all these experi- 
ments. It seems worth while to digress for a moment and men- 
tion here the circumstances under which he worked out the 
technique of practical sterilization by discontinuous heating, 
known today as 'TyndaUization/* He had been much impressed 
by the enormous resistance to heat exhibited by the spores of 
the hay bacillus, an organism universally present in hay infusions. 
Knowing that vegetative bacteria are easily killed by boiling and 
that a certain latent period is required before the heat-resistant 
spores return to the vegetative state in which they again become 
heat susceptible, he devised a process of sterilization which he 
first described in 1877 in a letter to Huxley: "Before the latent 
period of any of the germs has been completed (say a few hours 


after the preparation of the infusion), I subject it for a brief in- 
terval to a temperature which may be under that of boiling water. 
Such softened and vivified germs as are on the point of passing 
into active life are thereby kiled; others not yet softened remain 
intact. I repeat this process well within the interval necessary 
for the most advanced of those others to finish their period of 
latency. The number of undestroyed germs is further diminished 
by this second heating. After a number of repetitions which 
varies with the characters of the germs, the infusion however 
obstinate is completely sterilized." Boiling for one minute on 
five successive occasions could render an infusion sterile, whereas 
one single continuous boiling for one hour might not. 

It is likely that Pasteur's and TyndalTs triumph over the up- 
holders of the doctrine of spontaneous generation was not as 
universal and as complete as now appears through the perspec- 
tive of three quarters of a century. There must have been many 
scientists who, while accepting the wide distribution of microbes 
in the atmosphere, could not dismiss the belief that elementary 
microscopic life does now and then arise de nova from putre- 
fying matter. Indeed all over the world, there are today experi- 
menters watching with undying hope for some evidence that 
matter can organize itself in forms stimulating the characteristics 
of life. Man will never give up, and probably should not relin- 
quish, his efforts to evoke out of the chaotic inertia of inanimate 
matter the dynamic and orderly sequence of living processes. 

It was an unexpected event which revealed to Pasteur that, 
deep in the hearts of some of his most illustrious colleagues, the 
"chimera" of spontaneous generation was still breathing. 

The French physiologist Claude Bernard died in the fall of 
1877. Although it appears likely that his social intercourse with 
Pasteur never went beyond official meetings at the academies, 
the two men had enjoyed friendly scientific relations and had 
written in flattering terms of each other. There had been rumors 
that Bernard had devoted much of his last months of activity, 
in his country home of Saint-Julien, to the problem of alcoholic 


Iii fact, sketchy notes outlining a few crude experi- 

with the fermentation of grapes were found in 

the of a drawer after Ms death, and they were iname- 

by Bernard's friends, the chemist Berthelot and 

the physiologists Bert and d'Arsonval. Bernard stated in these 

that, contrary to Pasteur's views, fermentation could occur 

of living processes and he seemed to imply that 

yeast arise as a result of fermentation instead of being the 

of it Tfeast is produced only in those extracts of grape in 

which the protoplasmic function exists. It does not occur in the 

very young juice. It no longer occurs in the fuices which have 

rotted, in which the plasmatic power has been killed. . . /* 

Pasteur recognized in those obscure lines a disguised reappear- 
ance of the doctrine of spontaneous generation, and he expressed 
Ms dismay in a communication to the Academy: **On reading 
these opinions of Bernard, I experience both surprise and sorrow; 
surprise because the rigorous mind which I used to admire in him 
is completely absent in this physiological mysticism; sorrow, be- 
cause our illustrious colleague seems to have forgotten the demon- 
strations which I have presented in the past. Have I not, for exam- 
ple, carefully described as early as 1872, and more particularly 
in my Studies on Beer in 1876, a technique to extract grape juice 
from the inside of a beny, and to expose this juice in contact with 
pure air, and have I not shown that, under these conditions, yeast 
does not appear and ordinary alcoholic fermentation does not take 
place? . . . 

"It has also been painful for me to realize that all this was tak- 
ing place under the auspices of our eminent colleague M. 

Pasteur could not leave unanswered the veiled hint that yeast 
might after all originate from grape juice. Even though Ber- 
nard's posthumous statement could hardly be construed as any- 
thing more than a vague suggestion, the immense prestige of its 
author was enough to give new life to the lingering doctrine of 
spontaneous generation. For this reason, he immediately decided 
to demonstrate once more that alcoholic fermentation was de- 


pendent upon the prior introduction of yeast cells into the grape 
Juice, and this project naturally led Mm into the question of the 
origin of yeast under the natural conditions of wine making. 

The wine maker does not need to add yeast to start wine fer- 
mentation. The wild yeasts which are present in large numbers on 
the grapes and their stems are mixed with the grape juice at the 
time of pressing and they initiate lively fermentation shortly after 
the grape juice has been loaded into the vats. Depending upon 
the localities and the type of grapes, the wild yeasts differ in 
shape and physiological characteristics as well as in the flavor 
which they impart to the liquids they ferment The same kind of 
yeasts reappear at the appointed place in the vineyard every 
year, ready to start the fermentation of the new grape crop. It 
would seem, indeed, as if Providence had provided yeast to com- 
plete in a natural process the evolution of the ripe grape into fer- 
mented wine. Yeast almost appears as a normal component of 
the grape crop, and unf ermented grape juice as the crippled and 
mutilated fruit of the sunny vineyards. Where do these wild 
yeasts come from, and what are the workings of the time clock 
by which Providence brings them to the grape at the right time? 

Yeast cells are present in significant numbers on the plant only 
at the period when the grape ripens; then they progressively de- 
crease in number on the stems remaining after the harvest, and 
finally disappear during the winter. Pasteur's discovery that ripe 
grape carries its own supply of yeast explained the rapid course 
of fermentation under the practical conditions of wine making. 
It accounted also for some of the laboratory observations that 
had been quoted to support the theory of spontaneous generation, 
particularly for the fact that Bernard had observed the formation 
of some alcohol in the clear juice extracted from crushed grapes. 
All these conclusions had been anticipated in the Studies on Beer 
but, as Bernard had ignored or forgotten item, Pasteur resolved 
to repeat his earlier experiments on a larger and more convincing 
^cale. In addition to its scientific interest, this episode has the 
merit of illustrating Pasteur's working methods, his ardor in re- 
turning to already conquered positions when they were threat- 


the he decisions when he 

an at stake. His plan was for- 

the very clay the posthumous publication of 

"Without too much care for expense," he 

wrote, **I in all several hothouses with the intention 

of them to the Jura, where I possess a vineyard some 

of meters in size. There was not a moment to lose. 

And is why, 

"I have shoivn, in a chapter of my Studies on Eeer y that the 
germs of yeast are not yet present on the grape berry in the state 
of verjuice, which, in the Jura, is at the end of July. We are, I 
said to myself, at a time of the year when, thanks to a delay in 
growth due to a cold rainy season, the grapes are just in this state 
in the Arbois country. By taking this moment to cover some vine 
with hothouses almost hermetically closed, I would have, in 
October at grape harvest time, vines bearing ripe grapes without 
any yeasts on the surface. These grapes, being crushed with the 
precautions necessary to exclude yeast, will be able neither to 
ferment nor to make wine. I shall give myself the pleasure of 
taking them to Paris, of presenting them to the Academy, and of 
offering some clusters to those of my confreres who still believe 
in the spontaneous generation of yeast 

*The fourth of August, 1878, my hothouses were finished and 
ready to be installed. . . . During and after their installation, I 
searched with care to see if yeasts were really absent from the 
clusters in the state of verjuice, as I had found hitherto to be the 
case. The result was what I expected; in a great number of ex- 
periments I determined that the verjuice of the vines around 
Arbois, and notably that of the vines covered by the hothouses, 
bore no trace of yeast at the beginning of the month of August, 

"For fear that an inadequate sealing of the hothouses would 
allow the yeasts to reach the clusters, I decided to cover a cer- 
tain number on each vine with cotton wrappings previously" 
heated to a temperature of about 150 C. . . . 

"Toward the tenth of October, the grapes in the hothouses were 


ripe; one could clearly distinguish the seeds through their 
and they were as sweet in taste as the majority of the grapes 
grown outside; the only difference was that the grapes under 
the cotton, normally black, were scarcely colored, rather viola- 
ceous than black, and that the white grapes had not the golden 
yellow tint of white grapes exposed to the sun. Nevertheless, 
I repeat, the maturity of both left nothing to be desired. 

"On the tenth of October, 1 made my first experiment on the 
grapes of the uncovered clusters and on those covered with the 
cotton, comparing them with some which had grown outside. 
The result, I may say, surpassed my expectation. . . . Today, 
afler a multitude of trials, I am just where I started, that is to 
say, it has been impossible for me to obtain one single time the 
alcoholic yeast fermentation from clusters covered with cotton. 

"A comparative experiment naturally suggested itself. The hot- 
houses had been set up in the period during which the germs are 
absent from the stems and clusters, whereas the experiments 
which I have Just described took place from the tenth to the 
thirty-first of October during the period when the germs were 
present on the plant. It was then to be expected that if I exposed 
hothouse clusters from which the cotton had been removed on 
the branches of vines in the open, these clusters . . . would now 
ferment under the influence of the yeasts which they could not 
fail to receive in their new location. This was precisely the result 
that I obtained." 

In the presence of these results, nothing was left of Bernard's 
inconclusive experiments. Once more, spontaneous generation 
had been ruled out of existence. Pasteur had to fight a few more 
oratorical battles in the Paris Academy of Medicine against the 
last articulate upholders of the doctrine, but after 1880 little more 
was heard of them except the lonely voice of Bastian, who con- 
tinued to proclaim his faith until the time of his death in 1910. 

It is unrewarding for a philosopher to demonstrate his thesis 
with too much thoroughness and too convincingly. His ideas soon 
become part of the intellectual household of humanity, and the 


which to be expended in establishing them 

are or their memory becomes somewhat boring. 

For this reason, one often reads and hears that Pasteur and Tyn- 

wasted much talent and energy in a useless fight, for the 

in spontaneous generation was dying a natural death when 

they took arms against it In reality, they had to overcome not 

only the teachings of the most eminent physiologists of the day, 

but also emotional prejudices based on philosophical convictions. 

Neither Pasteur nor Tyndall ever devised an experiment which 
could prove that spontaneous generation does not occur; they 
had to be satisBed with discovering in each claim of its occurrence 
experimental falacies that rendered the claim invalid. It was this 
ever-renewed necessity of discovering sources of error in the 
techniques of the defenders of spontaneous generation that made 
it necessary to reopen the debate time and time again, thus giv- 
ing the impression of endless and wasteful repetition. The prob- 
lem was clearly stated by Pasteur before the Academy of Medi- 
cine ia March 1875, at the occasion of a debate during which 
Poggiale had spoken disdainfully of his experiments on sponta- 
neous generation. "Every source of error plays in the hands of 
my opponents. For me, affirming as I do that there are no spon- 
taneous fermentations, I am bound to eliminate every cause of 
error, every perturbing influence. Whereas I can maintain my 
results only by means of the most irreproachable technique, their 
claims profit by every inadequate experiment" 

In addition to settling the controversy on spontaneous genera- 
tion, Pasteur's and TyndalTs effort served to establish the new 
science of bacteriology on a solid technical basis. Exacting pro- 
cedures had to be devised to prevent the introduction of foreign 
germs from the outside into the system under study, and also to 
destroy germs already present in it. Because of this necessity, the 
fundamental techniques of aseptic manipulation and of steriliza- 
tion were worked out between 1860 and 1880. Incidental to the 
controversy also, there were discovered many facts concerning 
the distribution of microorganisms in our surroundings, in air 
and in water. It was also found that the Hood and urine of normal 
animals and of man are free from microbes and can be preserved 


without exhibiting putrefying changes if collected with suitable 
aseptic precautions. All these observations constituted the con- 
crete basis on which would be built the natural history of mi- 
crobial life and, as we shall see, Pasteur saw in them many analo- 
gies which helped him to formulate the germ theory of disease 
and the laws of epidemiology. The controversy on spontaneous 
generation was the exacting school at which bacteriology became 
aware of its problems and learned its methodology. 

However, it must be emphasized that what had been settled 
was not a theory of the origin of life. Nothing had been learned 
of the conditions under which life had first appeared, and no 
one knows even today whether it is still emerging anew from 
inanimate matter. Only the simple fact had been established that 
microbial life would not appear in an organic medium that had 
been adequately sterilized, and subsequently handled to exclude 
outside contamination. The germ theory is not a philosophical 
theory of life, but merely a body of factual observations which 
allows a series of practical operations. It teaches that fermenta- 
tion, decomposition, putrefaction, are caused by living micro- 
organisms, ubiquitous in nature; that bacteria are not begotten 
by the decomposing fluid, but come into it from outside; that 
sterile liquid, exposed to sterile air, will remain sterile forever. 

It was this concept that Pasteur exposed in his Sorbonne lec- 
ture before an amphitheater overflowing with a fashionable 
audience come to hear from him a statement concerning the 
origin, nature and meaning of life. But wisely he refrained from 
philosophizing. He did not deny that spontaneous generation was 
a possibility; he merely affirmed that it had never been shown 
to occur. 

The words which he pronounced on that occasion constitute 
the permanent rock on which were built whole sections of bio- 
logical sciences: 

There is no known circumstance in which it can be affirmed 
that microscopic beings came into the world without germs, with- 
out parents similar to themselves. Those who affirm it have been 
duped by illusions, by ill-conducted experiments, by errors that 
they either did not perceive, or did not know how to avoid." 


The Biochemical Unity of Life 

As in religion we are warned to sliow our faith by 
works, so in philosophy by the same rule the system 
should be judged of by its fruits, and pronounced 
frivolous if it be barren; more especially if, in place 
of fruits of grape and olive, it bear thorns and briars 
of dispute and contention. 


IN 1860 Pasteur recognized that the microorganisms responsible 
for the butyric fermentation and for putrefaction can grow in the 
absence of oxygen. As we have seen, this discovery was a land- 
mark in the history of biological sciences. It revealed a new and 
unexpected haunt of life and it served as a powerful beacon to 
search into some of the most intimate mechanisms of the chem- 
istry of living processes. And yet Pasteur's discovery was imme- 
diately belittled. Some questioned the validity of his observations, 
although few took the trouble to attempt to duplicate them. 
Many sneered at the wording of his descriptions because, im- 
pressed by the motility of the organisms that he had seen, he had 
referred to them as "infusoria" to suggest their animal nature. 
It is true that Pasteur's lack of familiarity with the terminology 
of the naturalist often rendered him somewhat inaccurate in the 
description of biological phenomena. 1 But he had the genius to 

1 Pasteur was aware of this limitation, but did not worry about it as he 
considered that the knowledge of microorganisms was still too imperfect to 
justify formal systems of classification. ""It was on purpose that I used vague 
words: mucors, torula, bacteria, vibrios. This is not arbitrary. What would 
be arbitrary would be to adopt definite rules of nomenclature for organisms 
that can be differentiated only by characteristics of which we do not know 
the true significance." 

The word "microbe** was introduced in 1878 by a surgeon, Sedillot, in 


reach beyond the channel of specialized knowledge into the vast 
horizons of general biological laws, as illustrated by the follow- 
ing defiant words. "Whether the progress of science makes of this 
vibrio a plant or an animal is immaterial; it is a living being* 
which is motile, which lives without air, and which is a ferment/' 
Thus, Pasteur entered biology, not through the narrow doors of 
classification and nomenclature, but by the broad stream of 
physiology and function. It is one of the most remarkable facts 
of his career that, although trained as a pure chemist, he attacked 
biological problems by adopting, straightaway, the view that the 
chemical activities of living agents are expressions of their physio- 
logical processes. He steadfastly maintained this attitude even 
when it brought him into conflict with the chemists and physiolo- 
gists of his time who looked with mistrust upon any attempts to 
explain the chemical happenings of life in terms of vital forces. 

So rapidly did Pasteur adopt die physiological attitude, in its 
most extreme form, that it appears of interest to document the 
evolution of his concepts with a few dates. 

It was on February 25, 1861, that he reported for the first time 
the existence of the butyric acid organisms and their anaerobic 
nature and suggested at the same time a possible causal relation 
between life without air and fermentation. On April 12 of the 
same year, he mentioned before the Societ6 Chimique that yeast 
ferments most efficiently in the absence of air whereas it grows 
most abundantly in its presence. These observations led him to 
suggest again that there exists a correlation between Me with- 
out oxygen and the ability to cause fermentation. He also stated 
at the same time that, under anaerobic conditions, yeast respires 
with the oxygen borrowed from the fermentable substance. He 
presented the new theory of fermentation in more precise terms 
on June 17, 1861. "In addition to the living beings so far known 

the course of a discussion at the Paris Academy of Medicine, to designate any 
organism so small as to be visible only under the microscope. Pasteur him- 
self rarely used it, but preferred the expression "microorganisms." 

Nevertheless he suggested in 1882 that the science of microbial life be 
designated "microbie** or "microbiologie," words which he properly re- 
garded as less restricted in meaning than "bacteriologie/* 


. . can respire and feed only by assimilating free oxygen, 
to a class of beings capable of living without 
air by oxygen from certain organic substances which 

a slow and progressive decomposition during the process 
of utilization. This latter class of organized beings consti- 

tutes the ferments, similar in all particulars to those of the former 
class, assimilating in the same manner carbon, nitrogen and phos* 
pbates> requiring oxygen like them, but differing from them in the 
ability to use the oxygen removed from unstable organic combina- 
tions instead of free oxygen gas for their respiration/* The same 
view was again presented in the form of a more general biological 
law on March 9, 1863. "We are thus led to relate the fact of nutri- 
tion accompanied by fermentation, to that of nutrition without 
consumption of free oxygen. There lies, certainly, the mystery of 
all true fermentations, and perhaps of many normal and abnormal 
physiological processes of living beings."* 

It is clear that Pasteur arrived very early at a well-defined con- 
cept of the relation of fermentation to metabolic processes, and at 
a realization that this concept had very broad implications for the 
understanding of the chemical processes of life. Although this 
generalization is perhaps the most original and profound thought 
of his long career, he never devoted much time to the subject, 
and his contributions to it were only by-products of other pre- 
occupations, particularly of his studies on the technological as- 
pects of the fermentation industries. Most of his fundamental 
thoughts on the physiological aspects of fermentation were pub- 
lished in the Studies on Beer. This book, intended to serve as a 
guide to the brewing industry, illustrates in a striking manner 
the struggle for the control of Pasteur's scientific life that went 
on beneath the apparently logical flow ,of "his work: the ever- 
lasting conflict between his desire to contribute to the solution 
of the practical problems of his environment, and his emotional 
and intellectual urge to deal with some of the great theoretical 
problems of life. 


It was then a common belief that many molds and other micro- 
organisms can become transformed into yeast when submerged 
in a sugar solution, and thus give rise to alcoholic fermentation, 
Pasteur himself long remained under the impression that the 
vinegar organism (Mycoderma aceti) 9 which oxidizes alcohol to 
acetic acid in the presence of air, can also behave as yeast and 
produce alcohol from sugar under anaerobic conditions. As these 
beliefs were in apparent conflict with one of the fundamental 
tenets of the germ theory of fermentation, namely the concept 
of specificity, Pasteur devoted many ingenious experiments to 
prove or disprove their validity, and arrived at the conclusion that 
they were erroneous. Yeasts, he pointed out, are ubiquitous in 
the air, and were often introduced by accident into the sugar solu- 
tions along with the other microbial species under study. It was 
therefore necessary to exclude this possibility of error, and after 
succeeding in eliminating it by elaborate precautions, he stated 
with pride, "Never again did I see any yeast or an active alcoholic 
fermentation follow upon the submersion of the flowers of vine- 
gar, ... At a time when belief in the transformation of species 
is so easily adopted, perhaps because it dispenses with rigorous 
accuracy in experimentation, it is not without interest to note 
that, in the course of my researches on the culture of microscopic 
plants in a state of purity, I once had reason to believe in the 
transformation of one organism into another, of Mycoderma into 
yeast I was then in error: I did not know how to avoid the very 
cause of illusion . . , which the confidence in my theory of germs 
had so often enabled me to discover in the observations of others." 
There remained, however, one case of apparent transformation of 
a mold into yeast, accompanied by alcoholic fermentation, which 
seemed to be confirmed by experiment. 

In 1857, Bail had asserted that Mucor mucedo, a mold com- 
monly present in horse manure, induced a typical alcoholic fer- 
mentation if grown out of contact with air by immersion in a 
sugar solution. Instead of the long mycelial filaments that are 
characteristic of the mold growing in the presence of air, there 
were then produced chains of round or oblong cells which Bail 


for of brewer's yeast Pasteur confirmed Bail's 

and that alcohol and bubbles of carbon dioxide 

produced out of the sugar in the absence of air. But instead 
of these phenomena as a change of the Mucor into 

yeast, he recognized in them a manifestation of his physiological 
theory of fermentation. He found that the short cells of Mucor 
which fermented in the bottom of sugar solutions immediately 
recovered their typical myeelial morphology when allowed to 
grow again in the presence of air. Under these conditions, they 
destroyed the sugar by complete oxidation instead of converting 
it into alcohol. In other words Mucor mucedo? which looked and 
behaved Mke yeast under anaerobic conditions, resumed the as- 
pect and behavior of a mold when in contact with oxygen. Thus, 
in the case of this microorganism at least, there existed a striking 
correlation between morphological characteristics and biochemi- 
cal behavior. The phenomena observed by Bail were not due to 
a transformation of species, but represented a transformation in 
cell form as a result of adaptation to a new life. The alteration 
in form coincided with a change of functions and Bail's phe- 
nomenon was merely the expression of a functional plasticity of 
the cell, allowing it to become adapted to a new environment. 

Pasteur asked himself whether the counterpart of this situa- 
tion might not occur in the case of true yeast. In agreement with 
his preconceived idea, he found that indeed the morphological 
and physiological characteristics of yeast were also influenced by 
the conditions of growth. Yeast grew slowly and fermentation took 
a long time in the total absence of air but the amount of sugar 
transformed into carbon dioxide and alcohol per unit of yeast 
was then extremely high. For example, 0.5-0.7 gm. of yeast was 
sufficient to transform 100 gm. of sugar into alcohol in the ab- 
sence of air, a ratio of 1 to 150 or 1 to 200. On the other hand, 
as the amount of air admitted during fermentation was increased, 
the development of yeast became more rapid and more abundant, 
and the ratio of weight of sugar fermented to weight of yeast 
became smaller. When an excess of oxygen, was provided through- 
out the process, hardly any alcohol was formed, although the 


development of yeast was very abundant and the ratio of sugar 
consumed to yeast produced fell to 4 or 5. Some alteration of 
the morphological characteristics of the yeast also occurred con- 
comitantly with these dramatic changes in physiological behavior* 

The correlation between the morphology of the fungus Mucor 
and the conditions of growth had served as a guide to recognize 
a correlation of a more fundamental nature, namely the depend- 
ence of biochemical behavior upon the availability of oxygen. 
Once before in his life, Pasteur had given an example of this 
change in emphasis, from the morphological to the functional 
level, in order to achieve a broader interpretation of observed 
phenomena. As wiH be remembered, it was the recognition of 
morphological differences between hemihedric crystals of tartaric 
acid that had led him to postulate a relation between crystal 
morphology, molecular structure, and ability to rotate the plane 
of polarized light. With the progress of his crystallographic 
studies he had later become less concerned with crystal shape, 
and had looked upon optical activity as a more direct expression 
of molecular structure. Similarly, the alteration in morphology 
of Mucor had now made him aware of a more fundamental 
fact, namely that fermentation was the result of life without 

These examples help in understanding Pasteur's attitude toward 
morphological studies for the investigation of natural phenomena. 
Many students of the history of bacteriology, and even his dis- 
ciple Duclaux, have asserted that Pasteur was completely in- 
different to considerations of morphology, and some have seen 
in this fact an indication that he had little interest in biology. 
This interpretation appears unjustified. In all phases of his scien- 
tific life, Pasteur observed and described morphological charac- 
teristics as carefully as his training and natural gifts permitted 
him. However, because he always had a specific goal in mind and 
because this goal was in all cases the understanding or the control 
of a function, he used morphology only as a guide to the dis- 
covery of functional relationships. Although he never studied 
morphological characteristics for their own sake, he used mor- 


wherever it provided information useful for the descrip- 
tion of a system. For Mm, experimental techniques and proce- 
of observation were never an end unto themselves, but only 
to be used for the solution of a problem and to be aban- 
doned as soon as more effective ones became available. 

Pasteur had postulated in 1861 that fermentation was the 
method used by yeast to derive energy from sugar under 
anaerobic conditions. In 1872 he restated these views in more 
precise terms. "Under ordinary conditions, the heat (energy) 
necessary for development comes from the oxidation of foodstuffs 
(except in the case of utilization of solar light). In fermentation, 
it comes from the decomposition of the fermentable matter. The 
ratio of the weight of fermentable matter decomposed to the 
weight of yeast produced will be higher or lower depending upon 
the extent of action of free oxygen. The maximum will cor- 
respond to life with participation of free oxygen." 

This theory did not explain the known fact that access of a 
small amount of oxygen often increases the rate of production 
of alcohol by yeast, and that consequently oxygen must play a 
certain role in the fermentation process. To account for this 
apparent discrepancy between theory and fact, Pasteur postulated 
that respiration in the presence of oxygen permits the accumula- 
tion of reserve materials which are utilized under anaerobic con- 
ditions. Oxygen is beneficial because "the energy that it com- 
municates to the life of the cell is later used up progressively /* 
Tliis prophetic view, for which evidence would not be forthcom- 
ing until half a century later, was suggested to Pasteur by mor- 
phological considerations. He described with great detail the ap- 
pearance of youthfulness and of improved health and vigor in 
yeast exposed to oxygen. "In order to multiply in a fermentable 
solution deprived of oxygen, yeast cells must be young, full of 
life and health, under tie influence of the vital activity which 
they owe to free oxygen and which perhaps they have stored. 
. . . When the cells are older, they generate bizarre and mon- 
strous forms. Still older, they remain inert in a medium free of 


oxygen. It is not that these old cells are dead; for they can be 
rejuvenated in the same fluid after it has been aerated.** 

The calling of other problems, of duties which he considered 
more pressing, prevented Pasteur from pursuing very far the 
demonstration of these affirmations. Moreover, theoretical knowl- 
edge and experimental techniques were not adequate to permit 
at that time a convincing demonstration of his theory of fermen- 
tation. Realizing this fact, he predicted in a visionary statement 
that final evidence would have to come from consideration of 
thermodynamic relationships, a science which was yet in its in- 
fancy. "The theory of fermentation . . will be established . . . 
on the day when science has advanced far enough to relate the 
quantity of heat resulting from the oxidation of sugar in the 
presence of oxygen to the quantity of heat removed by yeast 
during fermentation." 

Although the understanding of the relation of oxygen to fer- 
mentation had been derived from the study of yeast, Pasteur was 
convinced that, with proper modifications, the new knowledge 
would be valid for all living cells. He stated, for example, that 
the truly anaerobic forms such as the butyric ferment "differ from 
yeast only by virtue of the fact that they are capable of living 
independently of oxygen in a regular and prolonged manner." 
Lechartier and Bellamy had shown in 1869 that the plant cells 
of ripe fruits transform a part of the sugar that they contain into 
alcohol if the fruits in question are preserved in an atmosphere 
of carbon dioxide. This observation suggested that alcohol pro- 
duction from sugar was a general property of plant protoplasm 
functioning in the absence of free oxygen. In a similar vein, 
Pasteur observed that, whereas plums kept in an open container 
took up oxygen and became soft and sweet, they remained firm, 
lost sugar, and produced alcohol if placed in an atmosphere of 
carbon dioxide. Time and time again he restated his belief that: 
"Fermentation should be possible in all types of cells. . . . Fer- 
mentation by yeast is only a particular case of a very general 
phenomenon. All living beings are ferments under certain con- 
ditions of their life . . ." 


The between respiration and availability 

of is not limited to microbiai plant eels. "Similarly, 

in economy, oxygen gives to cells an activity from which 

they derive, when removed from the presence of this gas, the 
faculty to act in the manner of ferments.*' 

Pasteur never engaged in experiments with animal tissues. It 
appears of peculiar interest, therefore, to quote the a priori 
views which he expressed concerning the metabolism of muscle: 

*(fl) An active muscle produces a volume of carbon dioxide 
larger than the volume of oxygen consumed during the same 
time . . . this fact is not surprising according to the new theory, 
since the carbon dioxide which is produced results from fermenta- 
tion processes which bear no necessary relation to the quantity 
of oxygen consumed. (I?) One knows that muscle can contract in 
inert gases . , . and that carbon dioxide is then produced. This 
fact is a necessary consequence of the life continued by the cells 
under anaerobic conditions, following the initial stimulus which 
they have received from the oxygen. . . . (c) Muscles become 
acid following death and asphyxia. This is readily understandable 
if ... fermentation processes go on after death in the cells, 
which function then as anaerobic systems/' 

Thus, Pasteur arrived at the conclusion that aE living cells, 
whatever their own specializations and peculiarities, derive their 
energy from the same fundamental chemical reactions. By select- 
ing yeast and muscle to illustrate this law, he anticipated modern 
biochemistry, not only in one of its most far-reaching conclusions, 
but also in its methodology, for the study of yeast and muscle 
physiology has provided much of our understanding of the chem- 
istry of metabolic processes. 

Surprisingly enough, these large implications of Pasteur's views 
on the essential biochemical unity of Hfe did not impress his con- 
temporaries and are not mentioned even by Duclaux, who of all 
disciples assimilated most completely the spirit of the master's 
discoveries. It is the more surprising that they did not imme- 
diately become integrated into the physiological thinking of the 
time, because they fitted so well into the prevalent desire to ex- 


plain physiological in terms of physlcochemical re- 

actions. Indeed, Llebig, with his generalizing mind, had 

prophesied the new era in biochemistry in Ms last memoir of 
1869, entitled On Fermentation the Source of Muscular 

Energy. By the irony of fate, it was Pasteur who first expressed 
in clear chemical terms the analogy between the metabolism of 
yeast and the workings of muscle, thus giving reality to the 
prophetic views of his great German rival. 

Pasteur reiterated time and time again that, as far as it had 
been observed, fermentation was a manifestation of the life of 
yeast, causally connected with its metabolism and growth; but 
most contemporary physiologists believed that it was caused by 
simple chemical forces and they refused to explain the phenome- 
non in terms of vital action. It is now clear that the physiological 
view of fermentation held by Pasteur, and the chemical theories 
defended by his opponents, were not incompatible but indeed 
were necessary for the completion of each other. And yet, be- 
cause Pasteur was convinced that fermentation could be more 
profitably considered as a function of life than as a chemical 
reaction, and because his opponents refused to meet him on this 
ground for reasons of scientific philosophy, there arose a battle 
of words in which many of the most vigorous minds of the nine- 
teenth century took part. As will become obvious on reading 
some of the statements made by the leading contestants, there 
was no real justification for this controversy. Minor adjustments 
would have sufficed to compose the differences between the pro- 
ponents of the two theories, merely the willingness to recognize 
that all natural phenomena can be profitably investigated at dif- 
ferent levels of integration. Nevertheless, this great debate is of 
historical interest in recalling the struggles out of which modern 
physiology has evolved. It also illustrates how slow and painful 
is the maturation of a scientific concept that appears simple to 
the following generation; and reveals that, like other men, scien- 
tists become deaf and blind to any argument or evidence that 
does not fit into the thought pattern which circumstances have 


led to follow. Truth is many-faceted, and the facet which 

one to see from any given angle and at any given time 

is often different from, but not necessarily incompatible with, 
that which appears to one approaching from a different direction. 
For this reason, as Goethe said: ^History must from time to time 
be rewritten, not because many new facts have been discovered, 
but because new aspects come into view, because the participant 
in the progress of an age is led to standpoints from which the 
past can be regarded and judged in a novel manner." 

Two decades earlier, the sarcasm and haughty edicts of Ber~ 
zeMus and Liebig tad silenced the voice of those who believed in 
the living nature of yeast. In the I860*s Pasteur's fighting tempera- 
ment had made many scientists somewhat fearful of denying in 
pubBc the vitalistic theory of fermentation. In science as in poli- 
tics, however, it is easier to silence than to convince the oppo- 
nents of a doctrine. That the vitalistic theory was still held in 
ill-repute was revealed to Pasteur when Marcellin Berthelot pub- 
lished, in 1877, the fragmentary and sibylline notes in which 
Gaude Bernard had expressed his belief that alcoholic fermen- 
tation could occur in the absence of living cells. Pasteur was 
certainly right in regarding these notes as tentative projects and 
thoughts that Bernard had never intended to publish, and he 
accused Berthelot of utilizing the authority of the illustrious 
physiologist without the latter's consent. Although he was then 
heavily engaged in the study of anthrax, he did not hesitate to 
undertake new experiments proving that Bernard's assertions 
were based on faulty observations and he led a vigorous attack 
against Bernard and Berthelot in the Academy. Thus began a 
weird controversy, in which one of titte main protagonists was in 
the grave and appeared only in the form of a few posthumous 

Throughout his meditations on the mechanism of physiological 
processes, Claude Bernard had attempted to find a compromise 
between two sets of facts that he believed characteristic of Mf e. 
On the one hand, all physiological phenomena proceed accord- 
ing to the same physicochemical laws which govern other nat- 


ural events. On the other hand, it is equally obvious that each 
living being has Its own characteristic potentiality of development 
which, prearranged in the ovum, is an expression of the properties 
of the species and appears to depend upon forces which operate 
at a higher level of organization. It is this dual concept that 
Bernard, lacking an explanation, nevertheless felicitously ex- 
pressed in a famous statement: a Admitting that vital processes 
rest upon physicochemical activities, which is the truth, the 
essence of the problem is not thereby cleared up; for it is no 
chance encounter of physicochemical phenomena that constructs 
each being according to a pre-existing plan, and produces the 
admirable subordination and the harmonious concert of organic 
activity. There is an arrangement in the living being, a kind of 
regulated activity, which must never be neglected, because it is 
in truth the most striking characteristic of living beings/* 

This concept greatly influenced Bernard's views of the phe- 
nomena of alcoholic fermentation. He regarded the growth and 
development of yeast as a result of synthetic processes regulated 
by the property of organization which is characteristic solely of 
life. As to the processes of organic destruction, they were ex- 
plained by simple physicochemical laws. According to Bernard > 
it was this purely destructive aspect of the activities of the ceE 
which presided over the return of dead matter to nature, and 
which, in the case of yeast, was responsible for the breakdown 
of sugar into alcohol and carbon dioxide. Despite their philo- 
sophical dressing, these views were essentially a modernized re- 
turn to Berzelius's and Liebig's earlier concepts. The chemical 
theory of fermentation had recently received some support from 
the discovery of enzymes, those complex components of living 
cells which catalyze certain organic reactions. Berthelot had dem- 
onstrated the existence in yeast of a soluble agent, the enzyme 
invertase, which was capable of splitting cane sugar and which 
retained its activity even after being extracted in a soluble form 
free of yeast cells. Was it not possible that yeast could also pro- 
duce another enzyme capable of converting sugar into alcohol, 
precisely as invertase broke down cane sugar? 


With this possibility in mind, Bernard planned experiments to 
demonstrate the production of alcohol and carbon dioxide with- 
out the intervention of yeast, by the natural play of forces ex- 
terior to the cell. Having the preconceived notion that fermen- 
tation was the result of cellular disintegration, he undertook to 
find the alcoholic enzyme in grapes which had begun to decay. 
He crushed ripe grapes and observed in the clear juice the pro- 
duction of alcohol within forty-eight hours, in the absence of 
yeast as he believed. In other experiments, it is true, he did find 
yeast globules in his fermenting juice but, confident that he had 
not introduced them from the outside, he came to consider the 
possibilities that yeast might be a consequence, and not the origin, 
of the whole process. So crude were his experiments that they 
serve only to demonstrate how unwillingly experimenters, how- 
ever great, will subjugate the shaping of their concepts to the 
hard reality of facts. 

With the most exacting technique, Pasteur disposed of Ber- 
nard's claims within a few weeks, and demonstrated once more 
the dependence of alcoholic fermentation upon the presence of 
living yeast. But his triumph was incomplete, for it was at the 
level of biochemical doctrine, and not at the level of fact, that 
Bertfaelot attempted to defend Bernard's point of view. Berthelot 
argued that, in final analysis, all biological processes are the re- 
sults of chemical reactions. Since several activities of living cells 
had been shown to be caused by enzymes capable of remaining 
active in solution, away from the cells which had produced them, 
it was likely that production of alcohol could also occur in the 
absence of living yeast cells. To this plausible hypothesis Pasteur 
could rightly answer that the theory that fermentation is cor- 
relative with the life of yeast did account for all the known facts, 
and was in conflict with none. He was extremely careful to define 
his position in these exact terms so careful, indeed, that his atti- 
tude suggested the skill of an attorney who knows how to use 
statements expressing the letter of the law, even though the cause 
which he defends is in obvious conflict with common sense. In 
this strange debate, during which the two opponents used pol- 


ished academic to accuse other of bad faith, the 

facts were on Pasteur's side, but history was to show that 

it was Berfhelot who was speaking the voice of future common 

Twenty years after the controversy, a new fact became avail- 
able, which established at one stroke the theory that Lleblg, 
Berthelot, Bernard and their followers had attempted to uphold 
by means of logic, analogy and bad experiments. In 1897, Biich- 
ner extracted from yeast a soluble fraction, wMch he called 
"zymase/* and which was capable of producing alcohol from 
sugar in the absence of formed, living yeast cells. It is unfortunate 
for the dignity of the scientific method that this epoch-making 
achievement was not the outcome of an orderly intellectual 
process, but the unplanned result of an accident Hans and 
Eduard Biichner were attempting to break up yeast by grinding 
it with sand in order to obtain a preparation to be used for thera- 
peutic purposes. The yeast juice thus obtained was to be em- 
ployed for animal experiments but underwent alteration rapidly. 
As the ordinary antiseptics were found unsuitable to prevent the 
growth of bacteria, Biichner added sugar in high concentration to 
the juice as a preservative. To his great surprise, an evolution 
of carbon dioxide accompanied by production of some alcohol 
took place immediately and it was the marked action of the juice 
upon the added sugar which revealed to him that fermentation 
was proceeding in the absence of living yeast cells. 

Despite the fact that the discovery of zymase was the result 
of an accident, chance appears as the main actor only in the last 
scene of this great drama. In reality, physiologists and chemists 
had long worked hard trying to release the alcohol-forming en- 
zyme from yeast, beginning in 1846 with Liidersdorff. Roux has 
reported that Pasteur himself had attempted to grind, freeze and 
plasmolyze the yeast cells with this purpose in mind, but all in 
vain; and many were those who, before and after Pasteur, also 
failed. Biichner was the fortunate heir of a long tradition of 
experience, which had made frrm aware of the problem and its 


As in the case of so many discoveries, the new phe- 
was brought to light, apparently by chance, as the result 
of an Investigation directed to other ends, but fortunately fell 
under the eye of an observer endowed with the genius that en- 
abled him to realize its importance and give to It the true inter- 

Biichner*s discovery inaugurated a new era in the study of 
alcoholic fermentation, and from It has evolved the analysis of 
physiological phenomena in terms of the multiple individual 
steps of intermediate metabolism. Proof of the existence of 
zymase constituted a violent setback for the physiological theory 
of Pasteur, and biochemists came to regard cells as bags of en- 
zymes performing this or that reaction without much regard to 
their significance for the life of the organism. Within a decade, 
however, a new point of view began to manifest itself; it was 
forcefully expressed by the German physiologist Rubner: "The 
doctrine of enzymes and their action must be brought into rela- 
tionship with living processes . . . modern literature offers no 
explanation of the part played by sugar fermentation; this is re- 
garded merely as a result of ferment action. Our knowledge from 
the biological standpoint cannot be satisfied by this statement; 
the life of an organism cannot consist only in the production of a 
ferment causing decomposition." 

It is obvious today that the chemical processes of the cell sub- 
serve functions, and that there always exists a relation between 
the chemical changes observed within a living organism and the 
varied activities of this organism. It is equally certain on the 
other hand that all chemical changes which go on within living 
cells are carried out by means of a machinery, consisting largely 
of enzymes, and powered by energy-yielding reactions, which 
can operate outside the cell and function independently of life. 
The physiological and the chemical theories of fermentation and 
metabolism are therefore both right, and both are essential to the 
description of living processes. In fact, even the combination of 
the two theories may not be sufficient to explain life, for life is 
more than its mechanisms and functions. It is characterized, as 


Claude Bernard always emphasized, by the integration and or- 
ganization which "produce the admirable sulx>rdination and the 
harmonious concert of organic activity." To define the nature and 

mechanisms of this mysterious organization will be the exciting 
venture of the generations to come. 

From our vantage point in time, it is now possible to recapture 
the general trend of the long series of experiments and debates 
from which has evolved the modern doctrine of fermentation 
chemistry. Lavoisier, Gay-Lussac and Dumas had utilized to the 
best of their talent quantitative chemical techniques to establish 
an approximate balance sheet describing the conversion of sugar 
into alcohol and carbon dioxide. Their equation, however, did 
not provide any clue as to the nature of the forces involved in 
the reactions. When Pasteur approached the problem in 1856, 
two conflicting views confronted each other. The belief that yeast 
was a small living plant, and fermentation an expression of its 
life, had been ably presented twenty years earlier by Cagniard 
de la Tour, Schwann, Kiitzing and Turpin. Their views had been 
silenced by Berzelius and Liebig, who taught that the disrup- 
tion of the sugar molecule was brought about by contact with 
unstable organic substances. Pasteur's experiments established 
beyond doubt that, under the usual conditions of fermentation, 
the production of alcohol was the result of the life of yeast in 
the absence of oxygen; fermentation was the process by which 
yeast derived from sugar the energy that it needed for growth 
under anaerobic conditions. 

Berthelot, who like Liebig had originally held that fermen- 
tation was caused by dead protein and that yeast acted by virtue 
of the protein it contained and not as a living agent, had now 
recast his views to take into account the facts demonstrated by 
Pasteur. The following statement, which Berthelot published in 
1860, defined in the clearest possible terms the role of the recently 
discovered enzymes in the chemical activities of the cells. 

"From the work of M. Cagniard Latour, and even more from 
that of M. Pasteur, it has been proved that yeast consists of a 


mycodermlc plant I consider that this plant does not act on 
smgar a physiological action but merely by means of 

ferments which it is able to secrete, just as germinating barley 
secretes diastase, almonds secrete emiilsin 5 the animal pancreas 
secretes pancreatin, and the stomach secretes pepsin, . . . In- 
soluble ferments, on the other hand, remain attached to the tis- 
sues and cannot be separated from them. 

"In short, in the cases enumerated above which refer to soluble 
ferments, it is clearly seen that the living being itself is not the 
ferment but the producer of it. Soluble ferments, once they have 
been produced, function independently of any vital act; this func- 
tion does not necessarily show any correlation with any physio- 
logical phenomenon. I lay stress on these words so as to leave 
nothing equivocal in my manner of picturing the action of soluble 
ferments. It is evident, moreover, that each ferment can be 
formed preferentially, If not exclusively, by one or another plant 
or animal; this organised being produces and increases the cor- 
responding ferment in the same way as it produces and increases 
he other chemically defined substances of which it is composed. 
Hence the success of M. Pasteur's very important experiments on 
the sowing of ferments, or rather, in my opinion, of the organized 
beings which secrete the actual ferments.'* 

Liebig, also, had now come to regard yeast as a small living 
plant. Despite the gross factual errors that they contain, his 
long and confused memoirs of 1869 remain of interest in show- 
ing his generalizing and philosophical mind attempting to arrive 
at a reconciliation between the vitalistic and the chemical theories 
of fermentation. 

"I admit,** he wrote, "that yeast consists of plant cells which 
corne into existence and multiply in a liquid containing sugar 
and an albuminoid substance. The yeast is necessary for fermen- 
tation in order that there may be formed in its tissues, by means 
of the albuminoid substance and the sugar, a certain unstable 
combination, which alone is capable of undergoing disrup- 
tion. . . . 

"It appears possible that the only correlation between the 


physiological act the of fermentation is the 

production by the living yeast cell of a which, be- 

cause of peculiar properties similar to the one exerted by emul- 
sin on salicin or amygdalin, brings about the decomposition of 
sugar into other organic molecules. According to this view, the 
physiological act would be necessary for the production of this 
substance, but would bear no other relation to fermentation." 
Pasteur expressed complete agreement with this statement. It 
is unfortunate, therefore, that Liebig spoiled the chance of com- 
plete understanding by refusing to admit that one could bring 
about fermentation by growing yeast in a synthetic medium free 
of extraneous albuminoid matter, a refusal that he based on the 
failure of his own attempts, as well as on irrelevant and trivial 
arguments "If it were possible to produce or to multiply yeast 
by adding ammonia to the fermenting fluid, industry would soon 
have taken advantage of this fact . . , but so far, nothing has 
been changed in the manufacture of beer.** 

Shortly thereafter, Traube also attempted to reformulate the 
mechanisms of fermentation by incorporating all the known facts 
within a single theory, in particular Pasteur's recent discoveries 
on the role of oxygen in the process: The protoplasm of plant 
cells is itself, or contains, a chemical ferment which produces 
the alcoholic fermentation of sugar; the effectiveness of this fer- 
ment appears to depend upon the presence of the living cell for 
no one, so far, has succeeded in extracting it in an active form. 
In the presence of air, this ferment oxidizes sugar by fixing oxygen 
onto it; when protected from air, the ferment decomposes sugar 
by transporting oxygen from one group of atoms of the sugar 
molecule to another group, thus giving on one side a product of 
reduction (alcohol), and on the other a product of oxidation 
(carbon dioxide). 9 * With this statement, again, Pasteur agreed, 
but in this case also he could not come to terms with Traube, 
who denied that yeast could grow and ferment with ammonium 
salts as sole source of nitrogen. 

Thus, despite the lack of direct experimental proof, the view 
that alcoholic fermentation was due to the chemical action of 


elaborated by the cell, and not directly to the 
vital processes of the cell, found supporters even among those 
who regarded yeast as a plant. Claude Bernard expressed this 
point of view in the following statement to his disciples: "Pas- 
teur's experiments are correct, but he has seen only one side of 
the question. . . . Hie formation of alcohol is a very general 
phenomenon. It is necessary to banish from fermentation the 
vitality of cells. I do not believe in it" On October 20, 1877, in 
the last laboratory notes written before his death, he again wrote 
that fermentation "is not life without air, for in air, as well as 
protected from it, alcohol can be formed without yeast. . . . 
Alcohol can be produced by a soluble ferment in the absence of 

While Pasteur's assertion that the production of alcohol was a 
manifestation of life remained uncontroverted by experience 
until 1897, it is clear that all leading physiologists of the time re- 
garded fermentation as caused by enzymes which, theoretically 
at least, could act independently of the life of the cell that pro- 
duced them. Pasteur himself had not ignored the possible role 
of enzymes. As already mentioned, he had even tried to separate 
the soluble alcoholic ferment from living yeast The statement 
of the problem appears in the most clear-cut terms as early as 1860 
in Ms first memoir on alcoholic fermentation. 

**. . . If I am asked what is the nature of the chemical act 
whereby the sugar is decomposed and what is its real cause, I 
reply that I am completely ignorant of it 

"Ought we to say that yeast feeds on sugar and excretes alco- 
hol and carbonic acid? Or should we rather maintain tihtat yeast 
produces some substance of the nature of a pepsin, which acts 
upon the sugar and then disappears, for no such substance is 
found in fermented liquids? I have nothing to reply to these hy- 
potheses. I neither admit them nor reject them; I wish only to 
restrain myself from going beyond the facts. And the facts tell 
me simply that all true fermentations are correlative with physio- 
logical phenomena." 


Again in 1878, he "I would not be at all surprised if I 

were the cells of yeast can produce a soluble alco- 

holic ferment," but he also pointed out, "Enzymes are always 
the products of life, and consequently the statement that fer- 
mentation is caused by an enzyme does not contribute to our 
further understanding of the problem as long as no one has 
succeeded in separating the fermentation enzyme in an active 
form, free of living cells/* Because of this constant and overbear- 
ing emphasis on the aspects of the problem which had already 
been proved, and of this contempt for speculations which did not 
lead to experiment, Pasteur's attitude will appear to some nar- 
row and unphilosophicaL At the same time, however, these very 
limitations made him the most effective worker of all the par- 
ticipants in the debate. To all theories and discussions he could 
reply by the facts that he had established and that became, in- 
deed, the basis of all subsequent discoveries. "One is in agree- 
ment with me if one accepts that, (1) true fermentation de- 
pends upon . . * microscopic organisms, (2) these organisms 
do not have a spontaneous origin, (S) life in the absence of oxy- 
gen is concomitant with fermentation.' 1 " 

Pasteur's reply to Liebig in 1871 reveals with pungency an 
attitude characteristic of the mind of the experimenter, who pro- 
ceeds from one limited scope to another, in contrast with that 
of the more speculative mind which attempts to arrive at an 
all-embracing concept by a broad intellectual process. "If you 
agree with me that fermentation is correlative with the life and 
nutrition of yeast, we agree on the fundamental issue. If this 
agreement exists between us, let us concern ourselves, if you 
wish, with the intimate cause of fermentation, but let us recog- 
nize that this is a problem far different from the first. Science 
proceeds by successive answers to questions more and more 
subtle, coming nearer and nearer to the very essence of phe- 

It is perhaps, fitting to conclude the account of this celebrated 
controversy, to which so many of the most vigorous minds of the 


nineteenth century contributed their genius, and also their share 
of human frailties, by quoting from a letter written to Duclaux 
by Liebig, in 1872, one year before his death. 

I have often thought in my long practical career and at 
my age, how much pains and how many researches are 
necessary to probe to the depths a rather complicated phe- 
nomenon. The greatest difficulty comes from the fact that 
we are too much accustomed to attribute to a single cause 
that which is the product of several, and the majority of 
our controversies come from that. 

I would be much pained if M. Pasteur took in a disparag- 
ing sense the observations in my last work on fermentation. 
He appears to have forgotten that I have only attempted to 
support with facts a theory which I evolved more than thirty 
years ago, and which he had attacked. I was, I believe, in 
the right in defending it There are very few men whom I 
esteem more than M. Pasteur, and he may be assured that I 
would not dream of attacking his reputation, which is so 
great and has been so justly acquired. I have assigned a 
chemical cause to a chemical phenomenon, and that is all I 
have attempted to do. 


The Diseases of Silkworms 

Let no man look for much progress In the sciences 
especially in the practical part of them unless natural 
philosophy be carried on and applied to particular 
sciences, and particular sciences be carried back again 
to natural philosophy. 


1 HE FIRST triumphs of microbiology in the control of epidemics 
came out of the genius and labors of two men, Agostino Bassi and 
Louis Pasteur, both of whom were untrained in medical or vet- 
erinary sciences, and both of whom first approached the prob- 
lems of pathology by studying the diseases of silkwonns. 

Although Bassfs findings exerted no detectable influence on 
Pasteur's later work, it is only fair, for the sake of historical justice, 
to salute in the romantic person of the great Italian the dawn 
of the science of infectious diseases. Agostino Bassi was not a 
trained scientist, but a public servant in Lodi with such a love 
of scientific pursuits that he sacrificed to them not only the physi- 
cal comforts of life but his eyesight, which he ruined by countless 
hours at the microscope. 

A disease known as mat del segno was then causing extensive 
damage to the silkworm industry in Lombardy. Bassi demon- 
strated that the disease was infectious and could be transmitted 
by inoculation, by contact, and by infected food. He traced it to 
a parasitic fungus, called after "him Botryfis bassiana, which in- 
vaded the tissues during the life of the worm and covered its 
dead body with a peculiar white effervescence containing the 
fungal spores. An exact understanding of the etiology of the dis- 


of its mode of dissemination allowed Bassi to work out 
to prevent its spread through the silkworm nurseries. 
After twenty years of arduous labor, lie published in 1836, under 
the title Del del .... an extensive account of his theo- 

retical and practical Endings. Then, forced to give up microscopic 
investigations by the onset of blindness, he began to work and 
write on agricultural subjects. He continued, however, to develop 
the view that contagion is caused by living parasites, and applied 
Ms theory to the infectious diseases of man, and to the related 
problems of antisepsis, therapy and epidemiology. Although un- 
able to see the bacterial agents of disease because of blindness, 
Bassi envisioned from Ms studies on the mat del segno the bac- 
teriological era wMch was to revolutionize medicine two decades 
after his death. 

Toward the middle of the nineteenth century a mysterious dis- 
ease began to attack the French silkworm nurseries. It reached 
disastrous proportions first in the southern districts. In 1853, silk- 
worm eggs could no longer be produced in France, but had to 
be imported from Lombardy; then the disease spread to Italy, 
Spain and Austria, Dealers procuring eggs for the silkworm breed- 
ers had to go farther and farther east in an attempt to secure 
healthy products; but the disease followed them, invading in turn 
Greece, Turkey, the Caucasus finally China and even Japan. 
By 1865, the silkworm industry was near ruin in France, and also, 
to a lesser degree, in the rest of Western Europe. 

Before describing the manifestations of the disease and the 
studies that led to its control, it may be useful to describe in 
Duclaux's words the techniques by which the silkworm is com- 
mercially raised on the leaves of the mulberry tree. 

Everybody knows, at least in a general way, the principal 
phenomena of the life of the silkworm: its birth from an egg, 
whose resemblance to certain plant seeds has led to its being 
given the name of "seed," its four "molts," or changes of 
skin during which the worm ceases to eat, remains motion- 
less, seems to sleep upon its litter, and clothes itself, under 


its old skin, with a new skin, which allows 

it to undergo further development The fourth of these 
molts is followed after two or three days by a period of 
extreme voracity during which the worm rapidly increases 
in volume and acquires its maximum size: this is called the 
"grande gorge This period ended, the worm eats no more, 
moves about uneasily, and if sprigs of heather on which it 
can ascend are present, it finds thereon a suitable place to 
spin its cocoon, a kind of silky prison which permits it to 
undergo in peace its transformation first into a ciirysalis, 
and then into a moth. In this cocoon, the body of the worm, 
emptied of all the silky matter, contracts and covers itself 
with a resistant tunic in the interior of which all the tissues 
seem to fuse into a pulp of homogeneous appearance. It is 
in the midst of this magma that, little by little, the tissues of 
the moth are formed and become differentiated. 

The moth has only a rudimentary digestive canal, for it 
no longer has any need of eating: the worm has eaten for it. 
It has wings, but, in our domestic races, it makes no use 
of them. It is destined only for the reproduction of the spe- 
cies, and the sex union takes place as soon as the moth comes 
out of the cocoon. The female then lays a considerable num- 
ber of eggs, which may reach six hundred to eight hundred. 
In the races that we call annual, which are the most sought 
after, this "seed** does not hatch until the following year and 
is delayed until the reawakening of vegetation, the spring 
of the following year. 

It is only when the grower wishes to induce the laying of 
eggs that he awaits this coming-forth from the cocoon, in 
which case the transformation of the worm into a moth re- 
quires about fifteen days. By adding thereto the thirty-five 
or forty days required for the culture of the worm, and the 
time necessary for the laying of the eggs, we see that the 
complete evolution of the silkworm, from the egg to the egg, 
is about two months. The period of industrial life is sensi- 
bly shorter. When the grower wishes to use only the co- 
coons, he must not wait until the moth, in coming forth, has 
opened them and thereby rendered them unfit for spinning. 
They are smothered five or six days after they have climbed 
the twigs of heather. That is to say, the cocoons are put into 
a steam bath, to kill the chrysalids by heat. In this case, 
scarcely six weeks separate the time of egg-hatching from 


the when the cocoons are carried to market, from the 
the sows to the time when he reaps. As, in 

former times, the harvest was almost certain and quite lu- 
crative, the Time of the Silkworm was a time of festival and 
of joy, in spite of the fatigues which it imposed, and, in 
gratitude, the mulberry tree had received the name of arbre 
for ? from the populations who derived their livelihood 
from it 

The disease that was BOW afflicting the French silkworm nurs- 
eries was different from that studied by Bassi. It was usually 
characterized by the existence, within the worm and especially 
upon its skin, of very small spots resembling grains of black pep- 
per, and for this reason it was often referred to as "pebrine.** In- 
stead of growing in the usual uniform and rapid manner, from 
one molt to the other, the worms with pebrine became arrested 
at different stages of development. Many died in the first stages, 
and those which passed the fourth molt successfully could not 
complete their development, but instead faded away and gave 
imignilcant yields. However, it often happened that the worms 
showed the spots without being sick; and contrariwise, within a 
diseased group those worms which were not spotted did not neces- 
sarily give good cocoons or eggs. 

In addition to pebrine there were at the same time other forms 
of disease, known under the names "flacherie," marts-flats and 
gaMine, which riddled the French silk economy. They all had 
much in common and were considered probably different aspects 
of the same illness. Most frequently after the fourth molt, during 
the period of voracity called title grande gorge, the diseased worms 
were seen to be indifferent to the provender, crawling over the 
leaf without attacking it, even avoiding it, and giving the appear- 
ance of seeking a quiet corner in which to die. When dead, they 
generally softened and rotted, but sometimes remained firm and 
hard, so that one had to touch them to be certain that they were 
dead. When attacked more slowly by the disease, the worm 
climbed the heather, but with difficulty, slowly spun its cocoon, 
sometimes left it unfinished and died without changing into a 
chrysalis or a moth. 


The nature of pebrine was as mysterious as its origin. It 
loag been known that in the worms 

moths peculiar microscopic structures, designated as "corpuscles**; 
but these corpuscles could also be found in apparently healthy 
moths. There were several facts, nevertheless, which pointed to 
the relation of the corpuscles to the disease. In 1849 an Italian 
biologist, Osimo, had described them in the eggs of silkworms, 
and another Italian, Vittadini, had later stated that their numbers 
increased in proportion as the eggs approached the period of 
hatching. Convinced of the relation of the presence of corpuscles 
to the disease, Osimo had advised as early as 1859 that the eggs 
and chrysalids be examined microscopically with the aim of re- 
jecting the stocks found to be too corpuscular. This suggestion 
had been tested by still another Italian, Cantoni, who, having cul- 
tivated the eggs coming from noncorpuscular moths, had seen the 
worms develop corpuscular elements during the culture; this 
proved, Cantoni concluded, that the microscopic examination of 
moths was as worthless as the countless other remedies that had 
been advocated, and found wanting. 

At the request of Jean Baptiste Dumas, who came from one 
of the afflicted regions, the Minister of Agriculture appointed a 
mission for the study of pebrine. With an extraordinary foresight 
Dumas asked Pasteur to take charge of it. Although Pasteur knew 
nothing of silkworms or of their diseases, he accepted the chal- 
lenge under circumstances that have been described by Du- 

"I still remember the day when Pasteur, returning to the labo- 
ratory, said to me with some emotion in his voice, T>o you know 
what M. Dumas has just asked me to do? He wants me to go 
south and study the disease of silkworms.' I do not recall my 
reply; probably it was that which he had made himself to his 
illustrious master [Dumas] : Is there then a disease of silkworms? 
And are there countries ruined by it?* This tragedy took place so 
far from Paris! And then, also, we were so far from Paris, in the 
laboratory! 5 * To Pasteur's remark that he was totally unfamiliar 
with the subject, Dumas had replied one day: "So much the 


better! For ideas, you wiU have only those which shall come to 
you as a result of your own observations! 9 * 

Pasteur accepted Dumas*s request, in part because of Ms great 
devotion to his master. It is probable also that he welcomed the 
opportunity to approach die eld of experimental pathology, as 
is suggested by a sentence in his letter of acceptance; "The sub- 
ject . may even come within the range of my present studies." 
He had long foreseen that his work on fermentation would be of 
significance in the study of the physiological and pathological 
processes of man and animals. But he was aware of Ms lack of 
familiarity with biological problems and Dumas's insistence 
helped him to face an experience that he both desired and 

It is through his studies on the diseases of silkworms that Pas- 
teur came into contact with the complexities of the infectious 
processes. Surprisingly enough, he approached the problem un- 
ready to accept the idea that pebrine was caused by a parasitic 
agent foreign to the tissues of the worm. Instead, he retained for 
two years the belief that the disease was primarily a physiological 
disturbance, and that the corpuscles were only secondary mani- 
festations of it, products of disintegration of tissues. The intel- 
lectual struggle and blundering steps which led him to the con- 
cept that a foreign parasite was the primary etiological agent can 
be recaptured from two sources of information. One is the bril- 
liant analysis by Duclaux of the mental activities of his master 
during this period of their common labors. The other is found in 
the official documents prepared by Pasteur himself. As he was on 
a governmental mission and working under the public eye on a 
problem of great practical urgency, he had to make his results 
immediately available through official channels and his progress 
reports were naturally colored by the theoretical views he held 
of the nature of the disease. "In this phase of his researches," 
Duclaux points out, The had not the right to keep the Olympian 
silence with which he loved to surround himself until the day 
when his work appeared to him ripe for publication. Under nor- 
mal circumstances, he said not a word about it, even in the labo- 


ratory, where his assistants only the exterior and the skeleton 
of bis experiments, without any of the life which animated them. 
Here, on the contrary, he was under obligation as soon as he had 
found out something, to speak and to excite the public judgment, 
as well as that of industrial practice* oa al Ms laboratory dis- 

The struggle against error, always imminent in these studies on 
silkworm diseases, is of peculiar interest because it provides a 
well-documented example of the workings of a scientific mind. 
As Pasteur himself said: *lt is not without utility to show to the 
man of the world, and to the practical man, at what cost the 
scientist conquers principles, even the simplest and the most 
modest in appearance." Usually, the public sees only the finished 
result of the scientific effort, but remains unaware of the atmos- 
phere of confusion, tentative gropings, frustration and heart- 
breaking discouragement in which the scientist often labors while 
trying to extract, from the entrails of nature, the products and 
laws which appear so simple and orderly when they finally reach 
textbooks and newspapers. 

Pasteur arrived at Alais in early June and established primitive 
headquarters in a silkworm nursery. He immediately familiarized 
himself with the black spots of pebrine, and with the appearance 
of the corpuscles which were easy to find in the diseased worms 
and moths throughout the Alais district. As he began a systematic 
comparison of the appearance and behavior of different cultures 
{ broods ) of worms, there came his way an observation which sug- 
gested that the disease might well be independent of the presence 
of corpuscles. He found in a certain nursery two different cul- 
tures, one of which had completed its development and had as- 
cended the heather, while the other had just come out of the 
fourth molt The first one appeared healthy and behaved nor- 
mally; on the contrary the worms of the second ate little, did not 
grow and gave a poor harvest of cocoons. To his great surprise 
Pasteur found that whereas the corpuscles were abundant in the 
chrysalids and in the moths which had done well, they were 


in the of the bad culture. Further observation of 

the bad that the number of worms containing 

as the culture advanced; even more cor- 

were in the chiysailds, and finally not a single one 

of the was free of them. 

There appeared to be an obvious and inevitable conclusion to 
be drawn from these observations: namely that pebrine was fun- 
a physiological disturbance which weakened the 
worms, independent of the presence of the corpuscles, and that 
the latter constituted only a secondary and accidental expression 
of the disease, probably a breakdown product of tissues. What- 
ever their origin, however, the corpuscles could be used as an 
of the disease; and this led Pasteur to adopt again the 
method of egg selection that had been advocated by Osimo and 
found ineffective by Canton! He arrived at this conclusion within 
two weeks after his arrival at Alais, and recommended the egg- 
selection method in the following terms: The technique consists 
in isolating each couple, male and female, at the moment of egg- 
laying. After the mating, the female, set apart, will be allowed 
to lay her eggs; she should then be opened as well as the male, 
in order to search for the corpuscles. If they are absent both 
from male and female, this laying should be preserved, as it will 
give eggs absolutely pure which should be bred the following 
year with particular care." He described the same technique later 
in greater detail. "As soon as the moths have left their cocoons and 
mated, they should be separated and each female placed on a 
little square of linen where she will lay her eggs. The moth is 
afterwards pinned up in a comer of the same square of linen, 
where it gradually dries up; later on, in autumn or even in win- 
ter, the withered moth is moistened in a little water, pounded in 
a mortar, and the paste examined with a microscope. If the least 
trace of corpuscles appears, the linen is burnt, together with the 
seed which would have perpetuated the disease." 

As soon as the silkworm season was over, Pasteur moved back 
to Paris to resume his duties at the Ecole Nonnale. Early in Feb- 
ruary, 1866, he started again for Alais, accompanied by two assist- 


ants, Gemez and Maillot, and followed by Duclaux. After 

a short time, the party settled at Pont Gisquet, a lonely house at 
the foot of a mountain, and a laboratory was soon arranged in an 
empty orangery. 

Multiple tragedies afflicted Pasteur's life during these few 
months. In 1865 he had lost his father and one of his daughters, 
Camille, then two years old. Another daughter, Cecile, died of 
typhoid fever at the age of twelve during May 1866. As the weight 
of these sorrows and the burden of the immense responsibilities 
which he had undertaken were leaving a mark on his health, 
Madame Pasteur, accompanied by their last surviving daughter, 
Marie-Louise, came to join the hard-working group at Pont 

Comparative cultures of worms were immediately begun, with 
the eggs obtained the preceding summer from different pairs of 
moths which had exhibited corpuscles in varying degrees. Pre- 
liminary tests with small lots fed on the leaves of mulberry trees 
cultivated in hothouses were followed by the natural cultures in 
May and June. The results of these cultures revealed a number 
of facts of great importance. 

First, it became obvious that the larger the number of cor- 
puscles found in the parents of a given batch of eggs, the smaller 
was the yield of cocoons given by these eggs. There was no 
doubt, therefore, that the corpuscles bore a direct relation to the 
disease, even though it was not yet established that they were the 
cause of it. Very striking also was the fact that certain eggs laid 
by corpuscular moths remained capable of yielding acceptable 
cocoons, particularly eggs imported from Japan and those of a 
few sturdy French races. However, all the moths which origi- 
nated from these cocoons were strongly corpuscular and the fol- 
lowing generation of worms was, therefore, unsuited to the pro- 
duction of eggs and silk. This explained why selection of the 
seed from the gross appearance of the cocoon had given such 
unfortunate results and why it was necessary to know the extent 
of its contamination with corpuscles to judge of the value of an 
egg. Thus, additional evidence was obtained for the necessity of 


on microscopic study. Finally, it was recognized 
that, even in cultures derived from very corpuscular insects, one 
could here and there a few noncorpuscular moths which in 
their turn would produce healthy eggs. This observation meant 
that it was possible to recover a sound and productive stock from 
an infected nursery. 

Needless to say, many skeptics sneered at the suggestion that 
the microscope could ever become an effective tool in the con- 
trol of the disease. The microscope, they felt, might have its place 
in the hands of chemists, but how could one expect a practical 
silkworm grower to use such a complicated instrument? "There 
is in my laboratory,** answered Pasteur, "a little girl eight years 
of age who has learned to use it without difficulty." This little 
girl was his daughter, Marie-Louise, for at Pont Gisquet everyone 
had joined in the common task, and had become experienced in 
the art of growing silkworms. 

By June 1866 Pasteur was in a position to send to the Minister 
who had organized his mission in the South a statement that em- 
bodies the most important facts concerning the practical control 
of pebrine: 

Tn the past, the evil had been sought in the worm and even 
in the seeds, but my observations prove that it develops chiefly 
in the chrysalis, especially in the mature chrysalis, at the moment 
of the moth's formation, on the eve of the function of reproduc- 
tion. The microscope then detects its presence with certainty, 
even when the seed and the worm seem very healthy. The prac- 
tical result is this: You have a full nursery; it has been successful 
or it has not; you wish to know whether to smother the cocoons 
or whether to keep them for reproduction. Nothing is simpler. 
You hasten the development of about one hundred moths by 
raising the temperature, and you examine these moths through 
the microscope. 

The evidence of the disease is then so easy to detect that a 
woman or a child can do it. If the producer is a peasant, unable 
to carry out this study, he can do this; instead of throwing away 


the moths after they have laid their eggs, he can bottle them in 
brandy and send them to a testing office or to some experienced 
person who will determine the value of the seed for the f oHowing 

From then on, the egg-selection method was used systemati- 
cally in Pasteur's laboratory, and permitted the selection of 
healthy eggs. 

Why had Cantoni failed to obtain useful results with the same 
method? A similar question occurs again and again throughout 
Pasteur's scientific career. In many circumstances, he developed 
reproducible and practical techniques that in other hands failed, 
or gave such erratic results as to be considered worthless. His 
experimental achievements appear so unusual in their complete 
success that there has been a tendency to explain them away in 
the name of luck, but the explanation is in reality quite simple. 
Pasteur was a master experimenter with an uncanny sense of 
the details relevant to the success of his tests. It was the exacting 
conscience with which he respected the most minute details of 
his operations, and his intense concentration while at work, that 
gave him an apparently intuitive awareness of all the facts sig- 
nificant for the test, and permitted him always to duplicate his 
experimental conditions. In many cases, he lacked complete un- 
derstanding of the reasons for the success of the procedures that 
he used, but always he knew how to make them work again, if 
they had once worked in his hands. 

Although Pasteur had been adventurous enough to suggest the 
use of the egg-selection method on the basis of very sketchy ob- 
servations, he was well aware at that time of the inadequacy of 
the evidence available to prove that the corpuscles were a con- 
stant index of the existence of the disease in the worms. Where 
his predecessors had been satisfied with this uncertain state of 
affairs, he now decided to undertake comparative cultural experi- 
ments upon healthy and diseased eggs, in the hope of arriving 
at a more accurate knowledge of the relation of corpuscles to the 
disease. To this end he used the egg-selection method to secure 
seed originating from chrysalids containing varying numbers of 


So widespread was the in the Alais region, 

he was located, more than eight days of constant 
work were necessary to find among many hundred 
two or three pairs free of corpuscles. 

In a few preliminary experiments, Pasteur attempted to de- 
termine whether healthy worms would contract the disease when 
fed food contaminated with corpuscles, but the results had 
been equivocal; some of the worms had remained healthy, and 
others had died without exhibiting the corpuscles. A later experi- 
ment, carried out by Ms assistant Gernez, had been more instruc- 
tive. All the worms fed ordinary mulberry leaves, or leaves mois- 
tened with clean water, had yielded beautiful cocoons free of 
corpuscles. The worms fed with leaves contaminated with the 
debris of corpuscular moths had given only few cocoons, all very 
corpuscular, even when the contaminated leaves were first intro- 
duced after the third molting. Finally., the worms fed the con- 
taminated leaves only after the fourth molt gave a normal num- 
ber of cocoons, but most of these were corpuscular. 

Pasteur's assistants had become convinced that the corpuscles 
were the cause of the disease and they now believed that he also 
had reached the same conclusion- A new experiment of Gernez's 
appeared particularly convincing in this regard. It showed that 
worms issued from healthy eggs could give healthy cocoons, 
whereas the introduction of corpuscles either prevented the 
worms from reaching the cocoon stage if severe infection occurred 
early enough, or gave rise to corpuscular cocoons if the infection 
was delayed. When this experiment was reported to the Academy 
in November 1866, Gernez was much surprised to see Pasteur 
describe it merely as another evidence of the effectiveness of the 
egg-selection method, without even mentioning that the results 
suggested the contagious nature of the disease and the corpuscle 
as its cause. 

Duclaux claims that Pasteur had, in fact, failed to derive from 
the results of Gernez's experiments the conclusion that his dis- 
ciples had inferred. And yet, that he had given earnest thought 


to the possibility of infection is clear from a report that lie pre- 
sented two months later, in January 1867. To the "Is the 
disease parasitic?" he answered in the negative, for the following 

*(a) There are many circumstances in which the disease pre- 
cedes the corpuscles and therefore appears constitutional in 

"(b) The feeding of mulberry leaves contaminated with cor- 
puscular material, either in the form of dust from a silkworm 
nursery, or of ground-up moths or worms loaded with corpuscles, 
often kills the worms very rapidly without giving them the cor- 

"(c) I have not been able to discover a mode of reproduction 
of the corpuscles, and its manner of appearance makes it resemble 
a product of transformation of the tissues of the worms." 

Although these reasons indeed appeared sufficient to justify 
doubts concerning the role of the corpuscle as parasitic cause of 
the disease, they represented an erroneous Interpretation of ex- 
perimental findings. The first two points were invalidated by the 
fact, recognized by Pasteur himself the following year, that there 
was not one disease but two (or perhaps still more) occurring 
simultaneously in the same nursery and often in the same worm. 
Empirically., the silkworm growers had recognized this by using 
those different names pebrine, morts-flats, flacherie, gattine 
depending upon the symptoms of the diseased worms. No one, 
however, had yet extended these practical observations and postu- 
lated the existence of several different causal agents. 

It will be recalled that, during the first weeks of his studies, in 
1865, Pasteur had seen instances of diseased worms in which the 
corpuscles had appeared only in the late phases of the disease. It 
is almost certain, on the basis of present knowledge, that these 
worms had suffered first from the disease flacherie, and had only 
later become infected with the corpuscles of pebrine. Similarly, 
on several occasions when Pasteur had fed to healthy worms mul- 
berry leaves contaminated with corpuscular material taken from 
worms known to have pebrine, he had unwittingly introduced at 


the the causative agent of fiadberie. As the latter dis- 

ease often ran a much more rapid course than pebrine, many 
worms had sick, or even died, before the corpuscles had 

had time to multiply to detectable numbers. Thus, the first two 
arguments used by Pasteur to rule out the parasitic nature of the 
corpuscles were iirvalid because his observations dealt with pat- 
terns of disease other than of those of pebrine alone. 

The third reason given by Pasteur, namely his failure to recog- 
nize processes of reproduction of the corpuscles, was a penalty 
for Ms lack of knowledge of microscopic morphology. Pebrine, ii 
is now known, is caused by a protozoan parasite (Nosema bom- 
byds) which invades practically all the tissues of the embryo, 
larva, pupa and adult silkworm, and destroys the invaded cells. 
Pasteur's studies on fermentation and spontaneous generation had 
familiarized him with the morphology of yeasts and bacteria, 
which reproduce respectively by budding and binary fission 
{cleavage along the short axis), but the protozoan Nosema bom- 
byd$ undergoes a more complex morphological evolution. At a 
certain stage it penetrates the epithelial cells of the intestine of 
the worm, then becomes almost invisible before dividing again 
into distinct and sharply contoured corpuscles. Pasteur, who was 
a masterful observer, had detected under the microscope many of 
these morphological details, and had had them reproduced in a 
number of drawings to illustrate his memoirs. He described with 
precision the slow, progressive differentiation of the corpuscles 
out of tissue substances. However, being totally unfamiliar with 
protozoology, he failed at first to place the proper interpretation 
on his findings, and seeing the corpuscles appear as it were de 
novo in the midst of the tissues of the diseased worms, he con- 
cluded that the pebrine corpuscles were not independent elements 
but were the products of pathological transformation of diseased 

The scientific method is usually regarded as an orderly, logical 
process evolving from a correct interpretation of accurate find- 
ings to inescapable conclusions. It would seem that Nature had 
amused herself in this instance by leading Pasteur to a practical 


solution of the first problem of infectious disease that he tackled, 
through the peculiar pathway of complex observations and er- 
roneous interpretations. He, who had made himself the champion 
of the role of microorganisms in nature, denied for two years 
that the corpuscles were Mving parasitic agents, and stated that 
"pebrine is a physiological hereditary disease. 5 * 

During the 1866 season, Pasteur had prepared by egg selection 
large amounts of healthy eggs. He had used them in his own 
cultures and had also distributed them to many breeders for tests 
under practical conditions. Many of the results had fulfilled Ms 
expectations. However, it soon became obvious that certain 
batches issued from moths free of corpuscles gave disastrous re- 
sults, the worms dying rapidly with the symptoms of flacherie. 
Out of sixteen broods of worms which he had raised, and which 
presented an excellent appearance, the sixteenth almost perished 
entirely Immediately after the first molt. "In a brood of a hun- 
dred worms/* wrote Pasteur, **I picked up fifteen or twenty 
dead ones every day black, rotting with extraordinary 
rapidity. . . . They were soft and flaccid like an empty blad- 
der. I looked in vain for corpuscles; there was not a trace of 

The outbreaks followed a well-defined pattern. The new dis- 
ease attacked all the worms issuing from certain batches of eggs 
even though these eggs had been distributed to different 
breeders, who had raised them under various conditions of place, 
time, climate and culture. The worms were attacked at the same 
age, as if they had all brought with them an inescapable germ 
of destruction. The disease, clearly, came from the eggs, and not 
from the environment. Many of the worms dying of flacherie 
remained free of corpuscles and failed to exhibit the spots char- 
acteristic of pebrine. 

Pasteur became more and more anxious as he realized the 
gravity of the situation but, Duclaux says, "he kept us so remote 
from his thought that we could not explain his uneasiness until 
the day when he appeared before us almost in tears, and, drop- 


into a chair, said: 'Nothing is accomplished; 
are two diseases!* " 

We have already described,, in anticipation of this phase of 
Pasteur's studies, some of the characteristics of flacherie. Obvi- 
ously, the disease had been frequently associated with pebrine 
and had not been readily differentiated from it. As soon as pebrine 
could be eliminated by growing worms issued from noncorpuscu- 
lar moths 5 differential diagnosis of tie two diseases became pos- 
sible, and the road was opened for the study of lacherie. 

The etiology of flacherie is much more complex than that of 
pebrine, and Pasteur never succeeded in formulating a complete 
picture of it; indeed the cause of the disease is not clear even 
today. Instead of describing piecemeal the many detailed ob- 
servations made on the subject in the Pont Gisquet laboratory 
from 1866 to 1870, we shall summarize the point of view finally 
reached by Pasteur, although this involves the risk of presenting 
in terms of misleading simplicity a problem which must have ap- 
peared hopelessly confusing to the experimenters. 

Under normal conditions, the intestinal contents of the healthy 
silkworms are almost free of microorganisms. On the contrary, 
the digestive tracts of diseased worms contain immense numbers 
of bacteria of various types, spore-bearing bacilli and streptococci 
appearing to predominate among them. Contamination of the 
mulberry leaves with the excrement of diseased worms causes the 
appearance of the disease in healthy worms; the disease is, there- 
fore, contagious. Eggs derived from infected moths give rise to 
infected cultures., whatever the conditions under which they are 
raised, indicating either that the infection is carried in the egg or 
that certain batches of eggs exhibit a peculiar susceptibility to it. 

There was another puzzling observation. The disease now and 
then appeared spontaneously in a nursery, especially when tech- 
nical errors had been made in the handling of the mulberry leaves, 
or in controlling the temperature or aeration of the rooms. This, 
Pasteur believed, was because the disease agent was commonly 
distributed on the leaves; for he found that it was sufficient to let 
bruised mulberry leaves stand in high humidity at summer tern- 


perature to witness the development of similar to 

seen in the intestines of worms with fladberie, and to produce the 
disease in healthy worms fed on them. Pasteur concluded from 
these observations that the silkworms normally ingested a few 
bacteria with the leaves, but in numbers too small to establish a 
pathological state; at times, however, high temperature or exces- 
sive humidity or poor ventilation in the nursery allowed unusual 
multiplication of the bacteria on the leaves, and perhaps also 
caused a decrease in the physiological resistance of the worms. 
Under these conditions, Pasteur felt the bacteria gained the upper 
hand, and multiplied without restraint in the digestive organs; 
then the disease broke out 

Recent information suggests that the etiology of flacherie is 
even more complex, and that the primary cause of the disease 
belongs to the class of submicroscopic agents known as filtrable 
viruses, too small to be seen by ordinary microscopy. It is not 
unlikely that this hypothetical virus of flacherie can cause a dis- 
ease so mild that it escapes detection, but capable of rendering 
the silkworms more susceptible to a variety of bacteria eaten 
along with mulberry leaves; these bacteria might be the spore- 
bearing bacilli, or the streptococci seen by Pasteur in the intes- 
tines of the worms. In fact, the symptoms of the disease appear 
to vary, depending upon the nature of these bacterial invaders; 
and this variation probably accounts for the several different 
names under which the second disease of silkworms is known* 
gattine being the form in which Streptococcus bombyds pre- 
dominates, whereas BaciTlus bombycis occurs in the true flacherie. 
Several other mixed infections involving both a filtrable virus and 
a bacterium have been recognized in men and in animals during 
recent years. In the influenza pandemic of 1917-1918, for exam- 
ple, the primary cause of the infection was probably the influenza 
virus, which, alone, causes only a fairly mild disease but at that 
time the virus infection was complicated in many cases by a 
superimposed bacterial infection, which greatly increased its se- 
verity and modified its character. 

Pasteur did not, and could not, recognize and identify the mul- 


tiple factors that condition flacherie. However, thanks to the con- 
and penetrating supervision which he exercised over all the 
phases of the work in the experimental nursery at Pont Gisquet, 
lie a thorough knowledge of the manifestations of the dis- 

ease and of the factors which aggravated its course, and he soon 
succeeded in developing techniques to avoid its spread. 

Having become an expert breeder of silkworms, Pasteur could 
detect subtle differences in their behavior during the course of 
their development. In 1866, he had noted that in one of the cul- 
tures entirely free of pebrine, the worms had exhibited a peculiar 
behavior at the time of climbing up the heather to undergo trans- 
formation; they had appeared to him sluggish and unhealthy. Fol- 
lowing this lead, he secured silkworm cultures in which flacherie 
was prevailing, obtained from them cocoons free of pebrine cor- 
puscles, and confirmed that the eggs derived from these cocoons 
gave rise to cultures which failed almost entirely, especially in 
the fourth molt, with the characteristic symptoms of flacherie. 

On the basis of these observations, he formulated practical rules 
to prevent the development of the new disease. He emphasized 
**the imperious necessity of never using, for the egg laying 
whatever may be the external appearance of the moths or the 
results of their microscopic examination broods which have 
shown any languishing worms from the fourth molt to the cocoon, 
or which have experienced a noticeable mortality at this period 
of the culture, due to the disease of the marts-flats" Later, he 
also advocated a microscopic technique to detect the presence 
of bacterial infection in the moths used for the production of 
seed. The method consisted "in extracting with die point of a 
scalpel a small portion of the digestive cavity of a moth, then 
mixing it with a little water and examining it with a microscope. 
If the moths do not contain the characteristic microorganism, the 
strain from which they came may be considered as suitable for 

Thus, as in the case of pebrine, a practical solution had been 
found for the prevention of flacherie even before the cause of the 
disease had been thoroughly worked out. 


Most of the Investigations on silkworm diseases were carried 
out near Alms, one of the most important centers of die industry. 
From the beginning and through the five years of his campaign 
Pasteur established direct contact with the practical breeders, 
studying their problems at close range, concerning himself with 
the broad interests of the industry, and submitting his own views 
and methods to the acid test of application in the field. As we 
have seen, Pont Gisquet was not merely a research laboratory, it 
was an operating silkworm nursery where everybody, including 
Madame Pasteur and the little Marie-Louise, engaged in the 
raising of the worms and in the collection and selection of the 
eggs. Countless experiments and microscopic examinations; pains- 
taking control and watch over the trial cultures; worry over the 
ever-present threat of mice, which preferred silkworms to the 
most succulent baits; the feverish harvest of mulberry leaves 
when rain was threatening all these occupations left, to those 
who participated in the work, the memory of laborious days, but 
also that of one of the happiest periods in the scientific life of 
the master. 

Small lots of the seed, selected at Pont Gisquet, were tested in 
the laboratory and the balance distributed among producers who 
sent reports on the results of their cultures. This co-operative en- 
terprise soon led to an enormous volume of correspondence, 
which was handled by Pasteur himself. He spent his evenings 
dictating to his wife replies to distant collaborators, polemical 
articles for the trade journals, scientific articles for the academies 
and, finally, his book on the diseases of silkworms. 

There were then no typewriters, telephones, or efficient offices 
and secretaries. A photograph of Pasteur dictating a scientific 
note to his wife in a garden, with a large sun hat in the back- 
ground, calls forth a scene of olive trees and the brilliant skies of 
Provence, with cicadas humming their endless chant in the cool 
of the evening. It must have been good to work at Pont Gisquet, 
with an orangery for laboratory, and trees and water for office 

After the 1867 season, when techniques had been worked out to 
control the spread of pebrine and flacherie, it became more urgent 


to prove the practical character of the new method of silkworm 
In this work, Pasteur the qualities of a chief 

of industry who watches everything, lets no detail escape him, 
to know control all operations, and who ? at the same 
time, keeps up personal relations with his clientele, asking both 
who are satisfied and those who are not the reasons for their 
opinlOBS. To complete Ms apostolate, he became a practical silk- 
worm breeder; he traveled to the Alps and to the Pyrenees to 
supervise the installation of his process in the nurseries of grow- 
ers who had Implored his aid. 

There was., of course, much opposition to the new method, and 
to the personality of its discoverer. That a chemist should invade 
a purely biological Industry and try to modify ancestral practices 
appeared nonsense to some, and wounded the susceptibilities and 
prejudices of others. In addition to professional jealousies, there 
were the fears of the dealers in silkworm eggs, whose financial 
interests were threatened. Slanderous reports of the activities of 
the Pont Gisquet laboratory began to circulate through the peas- 
ant population and reached the newspapers. During June 1868, 
for example, Madame Pasteur received from her father a letter in 
which he expressed concern over their welfare. "It is being re- 
ported here that the failure of Pasteur's process has excited the 
population of your neighborhood so much that he has had to flee 
from Alais, pursued by infuriated inhabitants throwing stones 
at Mm." 

Pasteur responded to these attacks with his usual vigor. Every 
letter was acknowledged, whether friendly or threatening, every 
article answered with facts and also with passion. Addressing one 
who had questioned the value of the egg-selection program, Pas- 
teur concluded his argument with the edifying remark: "Monsieur 
le Marquis . . . , you do not know the first word of my investiga- 
tions, of their results, of the principles which they have estab- 
lished, and of their practical implications. Most of them you have 
not read . , . and the others, you did not understand." 

However, words and arguments were not sufficient to convince 
the unbelievers. Sure of his facts, Pasteur engaged in bold predic- 

Pasteur (approximately forty-five years old) at Pont Gisquet, 
dictating a scientific paper to his wife 


tions of the outcome of the cultures issued from which he 

had selected, or which he subjected to microscopic examina- 
tion. In February 1867, for example, he sent to the trade Journal 
Jean-Jean a prognosis^ to be opened only at the end of the season, 
of results on certain batches of eggs, and the prognosis turned 
out to be true. 

In IS68, he wrote to the Mayor of Callas, who had submitted 
two samples of eggs for examination: These two batches will fail 
completely, whatever the skill of the breeders and the importance 
of their establishment.*" 

The Silk Commission of Lyons, while interested in the selection 
method, had expressed some reserve as to its dependability, and 
had asked Pasteur in March 1869 for a little guaranteed healthy 
seed. He sent it, as well as other sample lots of which he predicted 
the future fate: 

1. One lot of healthy seed, which will succeed. 

2. One lot of seed, which will perish exclusively from the 
corpuscle disease known as pebrine. 

3. One lot of seed, which will perish exclusively from 

4. One lot of seed, which will perish partly from cor- 
puscle disease and partly from flacherie* 

It seems to me that the comparison between the results 
of those different lots will do more to enlighten the Commis- 
sion on the certainty of the principles I have established 
than could a mere sample of healthy seed. 

A few months later the Commission acknowledged the correct- 
ness of Pasteur's predictions. 

In April 1869, the Minister of Agriculture asked Pasteur to sub- 
mit a report on three lots of eggs that Mademoiselle Amat, a 
celebrated silkworm breeder, was distributing throughout the 
country. Pasteur's answer came four days later: 

. . . Monsieur U Mintetre . . . , these three samples of 
seed are worthless. . . . They will in every instance suc- 
cumb to corpuscle disease. If my seeding process had been 
employed, it would not have required ten minutes to dis- 


cover Mademoiselle Amat's cocoons, though excellent 
for purposes, were absolutely unfit for reproduc- 

tion, , . . 

I shall be much obliged, Monsieur le Ministre, if you wiH 

inform the Prefect of the Correze of the forecasts 

which I BOW communicate to you, and if you will ask him 

to report to you the results of Mademoiselle Amat's three 


For ray part, I feel so sure of what I now affirm, that I 
shall not even trouble to test, by hatching them, the samples 
which you have sent me. I have thrown them into the 
river. . . 

Marshal Vaiflant, Minister of the Emperor s household, finally 
conceived of a test that would establish the effectiveness of Pas- 
teur's method and silence his opponents. The Prince Imperial 
owned, near Triesta, an estate called Villa Vicentina, where 
pebrine and fiacherie had completely ruined the culture of silk- 
worms. In October 1869 the Marshal requested Pasteur to send 
selected seed and invited him to spend several months on the 
property. There he could supervise the raising of silkworms ac- 
cording to his methods, and at the same time recuperate from the 
attack of paralysis which had struck him the year before. Pasteur 
accepted the invitation, but instead of resting, completed his book 
on silkworm diseases, which was ready for publication in April 
1870. He spent the spring organizing the culture of his selected 
eggs, on the imperial property and in neighboring farms. Hie re- 
sults fulfilled aU expectations and the property paid a profit for 
the first time in ten years. The egg-selection method was gaining 
ever-wider recognition, and soon came to be applied on a large 
scale in Italy and Austria. 

The study on silkworm diseases constituted for Pasteur an 
initiation into the problem of infectious diseases. Instead of the 
accuracy of laboratory procedures he encountered the variability 
and unpredictability of behavior in animal life, for silkworms 
differ in their response to disease as do other animals. In the case 
of flacherie, for example, the time of death after infection might 


vary from twelve hours to three weeks, and some of the worms 
invariably escaped death. Pasteur repeatedly emphasized that 
the receptivity to infection of different individuals of the same 
species is of paramount importance in deciding the course and 
outcome of the disease. He also realized that the susceptibility 
of the worms was not solely conditioned by their inherited char- 
acteristics, but depended in part upon the conditions under which 
they lived. Excessive heat or humidity, inadequate aeration and 
stormy weather were all factors which he considered inimical to 
general physiological health of the worms, and capable of de- 
creasing their resistance to infection. Similarly, atmospheric 
conditions and poor handling could cause the spoilage of the mul- 
berry leaves and render them unfit as food. Even without attempt- 
ing to analyze the role of these factors, he learned to raise the 
worms under sanitary conditions by giving them enough space 
so that they would not infect each other, by isolating the diverse 
lots in separate baskets, by exposing them to the open air all 
practices which, in his mind, improved their well-being and pro- 
tected them against contagion. He devoted much thought to the 
engineering and architectural planning of the nurseries to provide 
hygienic conditions. As ever interested in the most minute details, 
he quoted that in China the woman in charge of the nursery, the 
"mother of silkworms,** was instructed to regulate the tempera- 
ture of the room according to her own feelings of warmth or 
cold when dressed in a traditional costume. 

Time and time again, he discussed the matter of the influence 
of environmental factors on susceptibility, on the receptivity of 
the "terrain** for tibe invading agent of disease. So deep was his 
concern with the physiological factors that condition infection 
that he once wrote, "If I had to undertake new studies on silk- 
worms, I would investigate conditions for increasing their vigor, 
a problem of which one knows nothing. This would certainly lead 
to techniques for protecting them against accidental diseases." 

He also kept constantly in mind the part played by the con- 
taminated leaves, equipment and dust in spreading the infection 
to the worms coming in contact with them. By thinking about 


problems, he discovered through direct experience many 
of the practices of epidemiology a knowledge that 

in stead when he began to deal with the diseases 
of animals and man, a few years later. 

He aware that this had been his apprenticeship into the 
study of pathological problems^ and he was wont to tell those who 
later came to work in his laboratory: * Read the studies on the 
silkworms; it will be, I believe, a good preparation for the inves- 
tigations that we are about to undertake." 


The Germ Theory of Disease 

A whole flock in the fields perishes from the disease 
of one. 


IT WAS In April 1877* that Pasteur published, in collaboration 
with Joubert, his first paper cm anthrax, twenty years after hav- 
ing presented the Manifesto of the germ theory in the memoir on 
lactic acid fermentation. One might be tempted to infer that these 
years had been necessary for the slow evolution and maturation, 
step by step and in a logical orderly manner, of the concept that 
microorganisms participate in the various processes of life and 
death. In reality, Pasteur had envisaged the role of micro- 
organisms in disease as soon as he had become familiar with 
the problem of fermentation, and had stated early his intention 
of applying himself to the study of contagion. 

While discussing the breakdown of plant and animal tissues 
by fermentation and putrefaction, he had written as early as 
1859: "Everything indicates that contagious diseases owe their 
existence to similar causes." In I860, he ventured the prediction 
that his studies on spontaneous generation and on the origin of 
microorganisms "would prepare the road for a serious investiga- 
tion of the origin of various diseases." After having demonstrated 
that microorganisms are present in the dust of the air and vary in 
type and number depending upon the location, the time and the 
atmospheric conditions, he suggested in 1861: TLt would be in- 
teresting to carry out frequent mioroscopic analysis of the dust 
floating in the air at the different seasons, and in different 


Hie understanding of the phenomena of contagion, 
during the periods of epidemic diseases, would have 
much to gain from such studies.** 

In a letter of April 1862 to the Minister of Education, quoted 
on page 161, he clearly indicated that contagious diseases were 
on Ms program of study; and again, in March 1863, he wrote to 
Colonel Fave, Aide-de-Camp to die Emperor: "I find myself pre- 
pared to attack the great mystery of the putrid diseases, which I 
cannot dismiss from my mind, although I am fully aware of its 
difficulties and dangers.** 

When in September 1867 he appealed to the Emperor for a 
new and larger laboratory, he emphasized the application of his 
studies on fermentation and putrefaction to the problem of dis- 
ease, pointing out that the handling of experimental animals, liv- 
ing and dead, would require adequate working facilities. Inter- 
estingly enough, he singled out in his request the subject of 
anthrax, although ten years were to elapse before his first experi- 
mental studies of this problem. 

The experience with silkworm diseases had greatly sharpened 
his awareness of the problems of epidemiology, and allowed him 
to recognize in apparently unrelated observations many lessons 
tfaat were applicable to the understanding of the spread of dis- 
ease, "In Paris, during the month of July when the fruit trade is 
active, there must be large numbers of yeasts floating in the air 
of the streets. If fermentations were diseases, one could speak of 
epidemics of fermentation." 

As we shall remember, Pasteur had found that wild yeasts 
become abundant in vineyards and on grapes only at the time 
of the harvest. Guided by this knowledge, he had succeeded in 
allowing grapes to ripen without coining into contact with yeast, 
by covering the vines early in the season with portable glass 
houses. The spores of the mold Mucor, on the other hand, were 
present in the vineyard throughout the year and therefore always 
contaminated the grapes despite the protection of the glass 
houses. It was from these simple facts that he casually formulated, 
in the following prophetic words, a statement that reads like a 


preview of the epidemiological laws of diseases: "Can 

we fail to observe that the further we penetrate into the experi- 
mental study of germs, the more we perceive unexpected lights 
and ideas leading to the knowledge of the causes of contagious 
diseases! Is it not worth noting that in this vineyard of Arbois . . . 
every particle of soil was capable of inducing alcoholic fermen- 
tation, whereas the soil of the greenhouses was inactive in this 
respect And why? Because I had taken the precaution of covering 
this soil with glass at the proper time. The death, if I may use 
this expression, of a grape berry falling on the ground of any 
vineyard, is always accompanied by the multiplication on the 
grape of the yeast eels; on the contrary, this kind of death is 
impossible In the comer of soil protected by my greenhouses. 
These few cubic meters of air, these few square meters of soil, 
were then in the midst of a zone of universal contamination, and 
yet they escaped it for several months. But what would be the 
use of the shelter afforded by the greenhouses in the case of 
the Mucor infection? None whatever! As the yeast cells reach the 
grape berries only at a certain time of the year, it is possible to 
protect the latter by means of a shelter placed at the proper time, 
just as Europe can be protected from cholera and plague by ade- 
quate quarantine measures. But the Mucor parasites are always 
present in the soil of our fields and vineyards, so that grapevines 
cannot be protected from them by shelters; similarly, the quaran- 
tine measures effective against cholera, yellow fever or plague 
are of no avail against our common contagious diseases." 

Thus, Pasteur had become convinced of the role of micro- 
organisms as agents of disease long before he had had any direct 
contact with animal pathology. One should not conclude, how- 
ever, that this prescience of the bacteriological era in medicine 
was an act of pure divination. Often in the preceding centuries, 
and especially during Pasteur's own time, natural philosophers 
and physicians had prophesied in more or less confused words 
that disease was akin to fermentation and to putrefaction, and 
that minute living agents were responsible for contagion. The 
story of the slow process by which men arrived at this concept 


forms a part of the Mstory of medicine, and cannot be told 

However, mention of a few of the milestones on this long 

will us to identify the intellectual straggles, and the 

of theories still in evidence during the second part of the 

Bmeteeath century, before the triumph of the germ theory of 


Test,** "cholera/* "malaria,* ^Muenza** in all languages these 
are words that evoke thoughts of terrifying scourges spreading 
over the land in a mysterious and inexorable manner. It was an 
awareness of the transmissibility of disease that led many early 
societies to formulate quarantine measures, in the hope of pre- 
venting contact with the sick or the introduction of the causative 
agents of epidemics. 

Physicians had pondered and argued endlessly on the origin 
and nature of contagion. Even for those who believed that dis- 
ease was a visitation by deities intent on punishing human sin 
and corruption, it remained no less a problem to comprehend 
how through what mechanism it could affect so many men 
in a similar manner at approximately the same time. Many as- 
sumed the prevalence during epidemic periods of certain telluric 
factors residing in die atmosphere, the soil, the waters, and the 
foods, which rendered most men susceptible to the scourge, as a 
drought causes the vegetation to wither, or as excessive exposure 
to the sun causes men to suffer sunstrokes. Ancient medicine was 
satisfied with this explanation, and codified It in the Hippocratic 
writings on "Air, Water and Places." Although science will cer- 
tainly return to the study of the telluric influences postulated by 
ancient biology, it is in another direction that European medicine 
turned in its effort to decipher the riddle of epidemic disease. 

It was early suspected that men could transmit a contagious 
principle to each other by direct emanations or bodily contact, 
or through the intermediary of clothing or of objects used in 
common. As early as the first century B.C., Varro and Columella 
had expressed the idea that disease was caused by invisible living 


things into the body with food or 

breathed in with air. 

The epidemic of syphilis which spread through all of Europe 
in the late fifteenth and early century gave many 

physicians frequent occasions to observe, often in the form of a 
personal experience, that a given disease can pass from one indi- 
vidual to another. In this case, the mechanism of transmission was 
sufficiently self-evident to give to the concept of contagion a 
definite meaning. It is an interesting coincidence that Fracastora, 
who coined the name "syphilis" in the sixteenth century, also for- 
mulated the first clear statement that communicable diseases were 
transmitted by a living agent, a contagium vtoum. In 1546, he 
described that contagion could occur by direct contact with the 
sick person, through the intermediary agency of contaminated 
objects, and through the air ad distant. He regarded the agents 
of disease as living germs, and expressed the opinion that the 
seeds of these agents could produce the same disease in all indi- 
viduals whom they reached. These essentially true statements 
were unconvincing, because they were not based upon a demon- 
stration of the physical reality of the hypothetical organisms, and 
confirmation of Fracastoro's theories was long delayed, even after 
the discovery of bacteria. 

Very early, analogies came to be recognized between certain 
disease processes and the phenomena of putrefaction and of fer- 
mentation. Just as contagious diseases were alterations of the 
normal animal economy communicable from one individual to 
another, similarly, different types of alterations and decay often 
appeared to spread through organic matter. Indeed, in the mak- 
ing of bread, a small amount of leaven taken from fermented 
dough could be used to bring about the rising of new dough, an 
obviously communicable change. Tenuous as these analogies 
were, they sufficed to induce many physicians and scholars to 
think and speak of fermentation, putrefaction, and communicable 
diseases in almost interchangeable terms, an attitude which was 
felicitously expressed in 1663 by Robert Boyle in his essay 


to the Part of 

He thoroughly understands the nature of ferments 
and fermentations, probably be much better able than 

he that Ignores them, to give a fair account of divers phe- 
nomena of several diseases (as well fevers as others) which 
will perhaps be never thoroughly understood, without an 
insight into the doctrine of fermentation. 
In fact, the concepts dealing with fermentation and contagious 
diseases foEowed a parallel evolution during the two centuries 
which folowed Boyle's statement In both cases, two oppos- 
ing doctrines competed for the explanation of the observed phe- 
nomena. According to one, the primary motive force be it of 
fermentation, putrefaction or disease resided in the altered 
body itself, being either self-generated, or induced by some 
chemical force which set the process in motion. According to 
the other doctrine, the process was caused by an independent, 
living agent, foreign in nature and origin to the body under- 
going the alteration, and living in it as a parasite. It is the con- 
flict between these doctrines which gives an internal unity to 
the story of Pasteur's scientific life. He took an active and decisive 
part in all phases of the conflict, and succeeded in uniting in a 
single concept those aspects of microbial life that have a bearing 
on fermentation, putrefaction and contagion. He was aware of 
the dramatic quality of this achievement and took pride in the 
fact that science had had to wait two centuries before Robert 
Boyle's prophecy became fulfilled in Pasteur's person. 

Among those who believed that certain minute living agents 
could pass from one individual to another, and transfer at the 
same time a state of disease, there were some who postulated that 
these carriers of contagion might be the small animalcules which 
the Dutch microscopist Leeuwenhoek had seen in the tartar of 
his teeth and in the f eces of man and animal. Leeuwenhoek's dis- 
coveries, made public by his letters to the Royal Society between 
1675 and 1685, had aroused much interest and assured him im- 
mediate as well as immortal fame. However, they remained with- 


out any real influence on for almost two 

centuries. In fact, it is questionable if any of the students of infec- 
tion before 1850 succeeded in visualizing how a microbial para- 
site could attack a large host and cause injury to it. 

Before the theory of contagion could gain acceptance it was 
essential that the various diseases be separated as well-defined 
entities. In the seventeenth century, Sydenham in London taught 
that there were species of diseases just as there were species of 
plants, and he gave lucid accounts of the differential diagnosis 
of contagious diseases such as smallpox, dysentery, plague and 
scarlet fever. However, Sydenham and his followers differentiated 
diseases only in terms of symptoms and did not attempt to classify 
them according to causes. With the growth of the knowledge of 
pathological anatomy, it became possible to base classification on 
the characteristics of the pathological lesions., and to begin in- 
quiry as to the causes of disease. The French clinician Breton- 
neau emphasized in the early nineteenth, century that *lt is the 
nature of morbid causes rather than their intensity which explains 
the differences in the clinical and pathological pictures presented 
by diseases." Bretonneau thought, furthermore, that specificity 
of disease was due to specificity of cause, and that each disease 
"developed under the influence of a contagious principle, capable 
of reproduction.** And he concluded, "Many inflammations are 
determined by extrinsic material causes, by real living beings 
come from the outside or at least foreign to the normal state of 
the organic structure." 

Surprisingly enough, Bretonneau did not even suggest that the 
causative agents capable of reproduction might be the micro- 
scopic organisms already so well known in his days, and he did 
not get beyond formulating a lucid but purely abstract concept 
of contagion. 

It is a remarkable coincidence that both the germ theory of 
fermentation and the germ theory of disease passed at exactly the 
same time from the level of abstract concepts to that of doctrines 
supported by concrete illustrations of their factual validity. 
Schwann, Cagniard de la Tour and Kiitzing had recognized simul- 


and independently in 1835-1S37 that yeast is a small 
plant, and fermentation a direct expression of its living 
In 1836 also Bassi had demonstrated that a fungus 
bassiana) was the primary cause of a disease of silk- 
worms. Shortly thereafter (1839) Schonlein found in favus the 
fungus since known as Achorion schonleinii, and another fungus 
Trichophytan tonsurans was shown in 1844 to be the cause of 
the Teigne tondante" (herpes tonsurans). Within a few years, 
several species of fungi were discovered as parasites of animal 
tissues and the parasitic role of these microorganisms achieved 
wide acceptance through the publication in 1853 of Robin's 
HMaire naturette des veg&taux parasites. 

A. few pathologists then began to reconsider the origin of con- 
tagious diseases in the light of the new knowledge. Prominent 
among them was Jacob Henle, who in his Pathologische Unter- 
suchungen formulated the hypothesis that "the material of con- 
tagion is not only organic but living, endowed with individual 
life and standing to the diseased body in the relation of a para- 
sitic organism." It is interesting to note that Henle was the inti- 
mate friend of Schwann (who had recognized in 1837 the living 
nature of yeast) and the teacher of Koch who, with Pasteur, 
was to substantiate the germ theory of disease a few decades later, 
Henle asserted that the demonstration of the causal role of a 
given microscopic agent in a given disease would require that 
the agent be found consistently in the pathological condition, 
that it be isolated in the pure state, and that the disease be re- 
produced with it alone. Robert Koch was the first to satisfy in 
the case of a bacterial disease namely anthrax all the criteria 
required by his teacher, and for this reason the rules so clearly 
formulated by Henle in 1840 are always referred to as "Koch's 

We have selected from the thought patterns of many centuries 
some of the shrewd guesses which led a few careful observers to 
formulate a correct statement of the mechanism of contagion, 
but it is certain that their views were not in line with the gen- 
erally held theories. While most physicians were willing to grant 


that certain as f avus, thrush 

and itch were produced by or plants, only a 

few believed that the important diseases like cholera, diph- 
theria, scarlet fever, fever, syphilis, could 
ever be explained in terms. 

The reaction of scientists to the pandemic of cholera that began 
to spread over Europe in 1846 puts in a clear light the prevailing 
confusion concerning the origin of epidemic diseases. Cholera 
was regarded by some as due to a change in the ponderable or 
imponderable elements of the air. Others regarded it as the result 
of a vegetable miasma arising from the soil, or of certain changes 
in the crest of the earth. Some held it was contagious, others that 
it came from animalcules existant in the air. From Egypt, the 
scourge had reached Paris, where its victims numbered more 
than two hundred daily during October 1865; it was feared that 
the days of 1832 would be repeated when the death rate 
reached twenty-three per thousand population. A French com- 
mission, consisting of Claude Bernard, Pasteur, and Sainte-Claire 
Deville, was appointed in 1865 to study the nature of the epi- 
demic; and Pasteur himself has told how the eminent scientists 
went into the attics of the Lariboisiere Hospital, above a cholera 
ward, in the hope of identifying in the air a poisonous agent re- 
sponsible for the disease. ce We had opened one of the ventilators 
communicating with the ward and had fitted to the opening a 
glass tube surrounded by a refrigerating mixture; we drew the 
air of the ward into our tube, so as to condense into it as many 
as we could of the air constituents." All this misconceived effort 
was of course in vain. 

The cholera epidemic, however, stimulated one study which 
appeared in agreement with the doctrine of contagium vivum. 
Having formed the belief that cholera begins with an infection 
of the alimentary canal, John Snow in London assumed that water 
might be the vehicle of transmission, and he verified his hypothe- 
sis by collecting exact data on a large number of outbreaks and 
correlating them with water supplies. At first ignored, his views 
gained ground following the spectacular Broad Street outbreak 


in 1554 IB London. Within two hundred and fifty yards from the 
spot where the disease began, there were five hundred deaths 
from cholera In ten days, at the end of which time the survivors 
took and the street was deserted. With unening exacti- 

tude. Snow traced the outbreak to the contamination of the water 
of a particular pump in Broad Street, and found in this water 
evidence of contamination with organic matter. Thus, even 
though John Snow did not deal with the ultimate cause of cholera, 
he clearly established that the epidemic was water-borne, and 
made it evident that some agent capable of surviving outside the 
body was concerned in its causation. 

Now that the concept of microbial parasitism has become so 
familiar even though so rarely understood it is difficult to 
realize why the medical mind remained impervious to the germ 
theory until late into the nineteenth century. Physicians prob- 
ably found it difficult to believe that living things as small as 
bacteria could cause the profound pathological damage and 
physiological disturbances characteristic of the severe diseases of 
animals and man. It was fairly easy to invoke parasitism to explain 
the invasion of the hair follicles by an insect, as in scabies; or of 
the skin surface by fungi, as in favus or herpes tonsurans; but 
there was something incongruous in a bacterium of microscopic 
size challenging and attacking a man or a horse. Moreover, it 
seemed ridiculous to assume that the specificity of the different 
disease processes could ever be explained in terms of these 
microbes, all apparently so similar in the simplicity of their shape 
and functions. Even today, the bacteriologist looks in vain for 
morphological or chemical characteristics that might explain why 
typhoid fever, bacillary dysentery, or food poisoning, for exam- 
ple, can be caused by bacterial species in other respects so alike 
that they can hardly be differentiated one from the other, or even 
from other bacteria that are not capable of causing disease. The 
modern physician is indoctrinated in the belief that certain con- 
tagious diseases are caused by microorganisms, but there was 
no reason for the physician of 1860 to have such a faith, which 


appeared in many with common sense. 

Under the leadersMp of Virchow in Germany* pathology was 
then achieving immense progress by recognizing and describing 
the alterations that different diseases cause in the various types 
of tissue cells composing the animal body. Every pathological 
modification was regarded as a physiological transformation, de- 
veloping in an organ which could not tolerate it, or at another 
time than the normal one. The secret of the disease appeared, 
accordingly,, to reside in the anatomy of the tissues. Furthermore 
the idea that there were organisms coming from the exterior 
which could impress specific modifications upon tissues was in 
disagreement with the general current of physiological science. 
A pleiad of illustrious physiologists Helmholtz, Du Bois-Rey- 
mond, Ludwig, Briicke had taken position against the exist- 
ence of a vital force, and were attempting to explain all living 
processes in terms of physicochemical reactions, just as Liebig 
was doing in the study of fermentations. The idea of the inter- 
vention of living microorganisms could not be received with 
sympathy and understanding in such an intellectual atmosphere. 
The germ theory of disease faced the same fundamental hostility 
which had stood in the way of the germ theory of fermentation. 1 
According to Liebig, Virchow, and their followers, the similarity 
between the causation of fermentation and contagious disease 
had its seat in the intrinsic properties of fermenting fluids or 
diseased cells, whereas Pasteur took the view that Boyle's pre- 
diction could be fulfilled by another unifying concept, namely 
the germ theory of fermentation and of disease. 

There is no doubt that Pasteur's demonstration, between 1857 
and 1876, that the "infinitely small" play an "infinitely great role" 
in the economy of matter prepared the medical mind to recognize 
that microorganisms can behave as agents of disease. The proof 

1 Many odd arguments were advanced to discredit the evidence derived 
from bacteriological science in favor of the germ theory. For example it was 
claimed that tests carried out in rabbits are not convincing, because "the 
rabbit is a melancholy animal to whom life is a burden and who only asks 
to leave it" (Quoted by H. D. Kramer in Bdl Hist. Med. 22 9 p. 33, 1948.) 


that fermentation and putrefaction were caused by fungi yeasts 
bacteria revealed a number of relationships which had their 
counterparts in the phenomena of contagion. It established that 
the effects of microorganisms could be entirely out of proportion 
to their size and mass and that they exhibited a remarkable 
specificity., each microbial type being adapted to the perform- 
ance of a limited set of biochemical reactions. The microorganisms 
carried out these reactions as a result of their living processes, 
I Jiey increased in number during the course of the reaction, and 
thus could be transferred endlessly to new media and induce 
again the alterations over which they presided. 

A few physicians who had retained contact with the evolution 
of natural sciences were struck by the analogies between fer- 
mentation and contagion and saw in them a sufficient basis to 
account for the origin of disease. In 1850, Davaine (who was 
than assistant to Rayer in Paris) had seen small rods in the blood 
of animals dead of anthrax, but had failed to comprehend their 
nature and importance. Pasteur's brief note on butyric fermenta- 
tion made Davaine realize that microscopic organisms of a dimen- 
sion similar to that of the rods present in anthrax blood had the 
power of producing effects entirely out of proportion to their 
weight and volume. This gave him the faith that the rods of 
anthrax might well be capable of causing the death of animals, 
and led him into the investigations which we shall consider in 
a later part of this chapter. 

Pasteur's studies on spontaneous generation had aroused much 
interest throughout the scientific world, as we have shown; and 
his demonstration that different types of living germs are widely 
distributed in the atmosphere gave a concrete basis to the vague 
view that agents of disease could be transmitted through the air. 
Pasteur himself had repeatedly emphasized this possible conse- 
quence of his findings, but it was the work of Joseph Lister 
which first established the medical significance of Ms teach- 

Lister was the son of a London wine merchant who had made 
distinguished contributions to the development of the modern 


microscope. Although he was in surgery, he developed, 

probably under Ms father's influence, a lively continued in- 
terest in bacteriological problems. Long after he had achieved 
international fame for Ms work on antiseptic surgery, he contrib- 
uted theoretical and technical papers of no distinction to 
the science of bacteriology. Lister was a young surgeon in Glas- 
gow when the impact of Pasteur's studies on the distribution of 
bacteria in the air convinced Mm of the role of microorganisms 
in the varied forms of **putric intoxications" which so commonly 
followed wounds and surgical interventions. Around 1864, he 
developed the use of antiseptic techniques in surgery with the 
object of destroying the microorganisins that he assumed to be 
responsible for the suppurative processes. Lister's methods, at 
first criticized and ridiculed particularly in England were 
progressively accepted, and became a powerful factor in trans- 
ferring the germ theory from the experimental domain to the 
atmosphere of the clinic. In a most generous manner Lister often 
acknowledged publicly his intellectual debt to Pasteur, for exam- 
ple in the following letter that he wrote to him from Edinburgh in 
February 1874: 


Allow me to beg your acceptance of a pamphlet, which I 
sent by the same post, containing an account of some inves- 
tigations into the subject which you have done so much to 
elucidate, the germ theory of fermentative changes. I flatter 
myself that you may read with some interest what I have 
written on the organisms which you were the first to de- 
scribe in your Memoire sur la fermentation appelee lactique. 

I do not know whether the records of British Surgery ever 
meet your eye. If so, you will have seen from time to time 
notices of the antiseptic system of treatment, which I have 
been labouring for the last nine years to bring to perfection. 

Allow me to take this opportunity to tender you my most 
cordial thanks for having, by your brilliant researches, 
demonstrated to me the truth of the germ theory of putre- 
faction, and thus furnished me with the principle upon 
which alone the antiseptic system can be carried out. Should 
you at any time visit Edinburgh it would, I believe, give you 


sincere gratification to see at our hospital how largely man- 

is being benefited by your labours. 

I eeed hardly add that it would afford me the highest 
gratification to show you how greatly surgery is indebted 
to you. 

Forgive the freedom with which a common love of science 
inspires me, and 

Believe me, with profound respect, 

Yours very sincerely, 


Lister again gave generous recognition to Pasteur in the intro- 
duction to his classical paper "On the Antiseptic Principle in the 
Practice of Surgery"; "When it had been shown by the researches 
of Pasteur that the septic property of the atmosphere depended, 
not on the oxygen or a gaseous constituent, but on minute or- 
ganisms suspended in it, which owed their energy to their vital- 
ity, it occurred to me that decomposition in the injured part 
might be avoided without excluding the air, by applying as a 
dressing some material capable of destroying the life of the float- 
ing particles." 

It is probable, although less certain than was believed by Pas- 
teur, that his studies on the alterations of vinegar, wine and beer 
had some influence on medical thought The very use of the word 
"diseases'* (maladies) to describe these alterations rendered more 
obvious the suggestion that microorganisms might also invade 
human and animal tissues, as they had already been proved to 
do in the case of silkworms. In opposition to the point of view 
expressed by the Paris clinician, Michel Peter, "Disease is in us, 
of us, by us, w Pasteur emphasized that contagion and disease 
could be the expression of the living processes of foreign microbial 
parasites, introduced from the outside, descending from parents 
identical to themselves, and incapable of being generated de 
novo. Time and time again he reiterated with pride his belief 
that the germ theory of fermentation constituted the solid rock 
on which had been erected the doctrine of contagious diseases. 
As early as 1877, at the very beginning of his studies on animal 


pathology, lie contemplated writing a book on the subject and 
described in a few manuscript notes the outline of the argument 
that he would have developed. 

"If I ever wrote a book entitled Studies on contagions or tram- 
missible diseases, ... it could properly begin by a reproduction 
of my memoir of 1862 (Memoir e sur les corpuscles organises 
qui existent dam Fatmosphere; Examen de la doctrine des 
generations spontanees) and of part of the whole of my memoir 
of 1860 (Memoir e sur la fermentation alcoolique), along with 
notes which would show at each step that this or that passage has 
suggested this or that memoir, this or that passage of Cohn, 
Lister, BiHroth, etc. . . . 

"Do not forget to emphasize in this book that medicine has 
been carried into the new avenues: 1. By the facts on putrefac- 
tion of 1863 (Examen du rdle attribue au gaz oxygene atmos- 
pherique dans la destruction des matieres animates et vegetates 
apres la mort. Recherches sur la putrefaction). 2. By the fact of 
butyric fermentation by a vibrio, a vibrio living without air; 
and the observations which I published on this subject . . . 
should be reproduced (Animalcules infusoires vivant sans gaz 
oxygene libre et determinant des fermentations. Experiences et 
vues nouvelles sur la nature des fermentations). 3. By my notes 
on wine diseases from 1864 on (Etudes sur les vins. Des altera- 
tions spontanees ou maladies des vins, particuMrement dans 
le Jura). Diseases of wines and microorganisms! What a stimulus 
this must have given to the imagination and intelligence; were it 
only through the connection between these words maladies and 

"Then in 1867, flacherie and its microorganisms. All this rest- 
ing on facts inassailable, absolute, which have remained in 
science. . . . Do not forget to point out that, in the preface of 
my studies on silkworms, there is mention of contagion, of con- 
tagious disease. . . " 

By 1875, the association of microorganisms with disease had 
received fairly wide acceptance in the medical world. Bacteria 


tad in many types of putrid wounds and other infec- 

tions. Obermeier had demonstrated in Berlin under Virchow's 
eyes the constant presence of spiral-like bacteria {spiro- 
chetes) in the blood of patients with relapsing fever. But the 
mere demonstration that bacteria are present during disease was 
not proof that they were the cause of it. As revealed by the dis- 
cussions in the Paris Academy of Medicine, there were still 
physicians who believed that microorganisms could organize 
themselves de novo out of diseased tissue. The belief in spon- 
taneous generation died hard in medical circles. More numerous 
were those who believed that bacteria, even introduced from the 
outside, could gain a foothold only after disease had altered the 
composition and properties of the tissues. For them, bacterial 
invasion was only an accidental and secondary consequence o 
disease^ which at best might modify and aggravate the symptoms 
and pathological changes, but could not be a primary cause. As 
will be remembered, a similar point of view had been held by 
Liebig, Helmholtz, Schroder and many others with reference to 
the role of bacteria in putrefaction. 

The germ theory of disease was also condemned in the name of 
plain common sense. Common sense is the expression of two un- 
related mental traits; it is based in part on the recognition of an 
obvious, direct relationship between certain events, uncom- 
plicated by theories. As such it has a pragmatic value and allows 
its possessor to behave effectively in ordinary situations. The same 
expression, "common sense/' is also used to express beliefs and 
opinions which are not the result of personal experience, but are 
only inherited along with the conventions which make up our 
everyday Me. It was because the germ theory was in conflict 
with these two forms of common sense that its acceptance was 
so difficult. 

The occurrence of contagious disease was known to be often 
associated with insalubrious living conditions, and the belief had 
been transmitted from Hippocratic time that the physical en- 
vironment decided the health of a community. This point of 
view was expressed forcefully by Florence Nightingale, the 


woman who, through her experience in military 
the Crimean War and in India, by virtue of her fighting tem- 
perament, did so much to make of nursing an part of 
medical care; 

"I was brought up by scientific men and ignorant women dis- 
tinctly to believe that smallpox was a of which there was 
once a specimen in the world, which went on propagating itself 
in a perpetual chain of descent, just as much as that there was a 
first dog (or first pair of dogs) and that smallpox would not 
begin itself any more than a new dog would without there hav- 
ing been a parent dog. Since then I have seen with my eyes and 
smelled with my nose smallpox growing up in first specimens, 
either in close rooms or in overcrowded wards, where it could 
not by any possibility have been c caught* but must have begun. 
Nay, more, I have seen diseases begin, grow up and pass into 
one another. Now dogs do not pass into cats. I have seen, for 
instance, with a little overcrowding, continued fever grow up, 
and with a little more, typhoid fever, and with a little more, 
typhus, and all in the same ward or hut. For diseases, as all 
experiences show, are adjectives, not noun substantives . . . 

"The specific disease doctrine is the grand refuge of weak, un- 
cultured, unstable minds, such as now rule in the medical pro- 
fession. There are no specific diseases: there are specific disease 

Despite the official and popular hostility to the germ theory, 
several physicians and veterinarians attempted to prove between 
1860 and 1876 that bacteria could by themselves initiate disease 
in a healthy body. Pasteur followed these efforts with eagerness 
but, we are told by Roux, "they caused him at the same time 
pleasure and worry. These experiments by physicians often ap- 
peared to hfm defective, their methods inadequate and the proofs 
without rigor, more likely to compromise the good cause than 
to serve it Soon he could no longer help himself and resolutely 
decided that he too would attack the problem of anthrax." 

This was in 1876. Unknown to him, a young German country 


doctor, Robert Koch, had embarked on the same venture the year 
and on April 30, 1876, had presented to Ferdinand Cohn, 
in the Botanical Institute in Breslau, the complete life history of 
the anthrax bacillus. 

Koch, then thirty-three years old, was practicing medicine in 
Wollstein in Posen. He had studied in Gottmgen and Berlin 
under distinguished scientists, most notable among them being 
the chemist Wohler and the pathologist Henle. From the latter, 
he had learned the difficulties which stood in the way of estab- 
lishing the germ theory of disease, and the exacting criteria which 
had to be met to prove the etiological role of a given bacterium. 
It was within the rigid framework of this experimental and in- 
tellectual discipline that Koch placed himself throughout his 
laborious studies of contagious diseases. Within a few years after 
working out the life cycle of the anthrax bacillus, he published his 
work on the Etiology of Traumatic Infective Diseases (1878) 
and achieved immortal fame by isolating the tubercle bacillus in 
1882, and the cholera vibrio in 188$. These spectacular achieve- 
ments, and the development of experimental and diagnostic 
techniques which are still universally employed today, soon made 
him the leader in Berlin of a school to which students from all 
over the world flocked to learn the methods of the new science 
of medical bacteriology. We shall not follow the meteoric career 
or describe the stern personality of the great German master, as 
he crossed Pasteur's path but a few times in the course of his busy 
and successful life. For the time being, we shall be content with 
describing how the work of the two founders of medical bacteri- 
ology met in the problem of anthrax, to establish once and for all 
the germ theory of disease. 

The story of the work on anthrax prior to Koch and Pasteur 
illustrates how great discoveries are prepared by the laborious 
efforts of the "unknown soldiers" of science. Of these forgotten 
workers some failed to win the final victory because they could 
not encompass in a single theme all the elements of the struggle, 
others because they arrived too early on the scene of combat, at 


a time when the ground had not yet sufficiently cleared to 

permit the marshaling of al the forces necessary for victory. 
But the part they played in commencing to clear the ground is 
often as important as the more spectacular achievements of those 
participating in the last phases of the battle. 

Rayer and Davaine in 1845 and Polender in 1855 had seen, in 
the blood and the spleen of cattle dead of anthrax, large numbers 
of microscopic, straight, nonmotile rods. Whereas the two French 
workers had failed to understand the significance of their observa- 
tion, Pollender had considered the possibility that the rods might 
be the contagious elements of anthrax but he did not succeed in 
ruling out the possibility that they were merely products of putre- 
faction. Further observations by Brauell in Germany appeared 
to favor the latter interpretation. Brauell had inoculated the blood 
of animals dead of anthrax into sheep and horses, and had 
searched for the appearance of the rods seen by Rayer, Davaine 
and Pollender. Like his predecessors, he had found them in the 
blood of many inoculated animals^ but often, and especially in 
blood kept for several days, the rods were different in shape from 
those described before, and furthermore they appeared actively 
motile. Pollender also observed that, In certain cases, horses 
injected with anthrax blood would die without showing any rods 
whatsoever in their blood. It appeared consequently that the rods 
were not the real cause of the disease, but only one of its acci- 
dental consequences. 

Two years later, Delaf ond pointed out that the motile bacteria 
seen by Brauell were not characteristic of true anthrax; they 
started to multiply in the blood only after putrefaction had begun 
to set in, following the death of the animal, precisely at the time 
when the anthrax rods described by Rayer, Davaine and Pollender 
began to disappear. Delafond was convinced of the living nature 
of the anthrax rods. In the hope of proving it, he let blood stand, 
expecting to see the rods undergo a complete evolution to what 
he called the seed stage, but detected only a limited increase in 
length of the rod structure in the course of several days. 

After reading Pasteur's work on the butyric vibrio in 1861, 


Davalne that the rods which he had seen in 

might, all, be the cause of the disease. By experimental 

Inoculations of and thorough microscopic studies, he 

arrived at a precise knowledge of the relation of true anthrax 

to the secondary processes of putrefaction. He based Ms belief 

the rods must be the cause of the disease on the fact that 

they were constantly present during the disease, that the disease 

could be transmitted by inoculation, and that there was no 

anthrax in the absence of the rods. 

Many workers, however, still questioned the validity of his 
conclusions and reported, in agreement with BrauelTs findings, 
that animals sometimes died without exhibiting the presence of 
the typical rods in their blood. Experiments carried out by two 
French workers, Leplat and Jaillard, are worth discussing in this 
respect as they stimulated Pasteur's first observations on anthrax. 
These two workers had inoculated anthrax blood into a large 
number of rabbits, but had never found any trace of Davaine's 
rods, notwithstanding the fact that their animals died; they 
naturally concluded that the rods were merely an epiphenomenon 
of the disease. 10 a discussion of their paper, Pasteur agreed with 
Davaine that the disease induced experimentally by Leplat and 
Jaillard was not anthrax, and that the cow from which they had 
obtained their original material had died of another septic dis- 
ease. To refute this, Leplat and Jaillard obtained blood from an 
animal which had unquestionably died of anthrax and which con- 
tained myriads of immobile rods similar to Davaine^s rods. Rab- 
bits inoculated with this blood died without showing any rods 
and yet their blood could cause death when injected into other 
rabbits. Thus, once more it appeared as if Davaine's rods were 
not the real cause of anthrax. Davaine pointed out again that 
the disease which killed the rabbits in Leplat and Jaillard's tests 
differed in its clinical course and pathological characteristics 
from true anthrax. Pasteur agreed with him after recognizing in 
the original blood used by Leplat and Jaillard putrefactive bac- 
teria and others similar to the butyric ferment, instead of Davaine's 


The physiologist Paul Bert was one of those who long re- 
mained unconvinced even after Koch's work. Believing that all 
living agents could be Idled by adequate pressures of oxygen, 
he exposed the blood of an animal dead of anthrax to the action 
of compressed oxygen, in order to Mil any living form that it might 
contain. Yet, inoculation of this blood produced disease and 
death, without the reappearance of bacteria. Therefore, Bert 
concluded, the bacteria were neither the cause nor the necessary 
effect of anthrax, 

It was in the midst of this confusion that Koch's classical paper 
appeared, describing in the most exquisite and complete details 
the life history of the anthrax bacillus and its relation to the 

Koch had frequent occasion to observe anthrax in farm animals 
in the course of his medical duties. Working in a primitive labora- 
tory that he built in his own home, he established the fact that the 
disease was transmissible from mouse to mouse and produced 
typical and reproducible lesions in each member of the successive 
series of mice. He had also the original idea of placing minute 
particles of spleens freshly removed from infected animals in 
drops of sterile blood serum or of aqueous humor, and he began 
to watch, hour after hour, what took place. His technique was 
simplicity itself, his apparatus homemade. After twenty hours he 
saw the anthrax rods grow into long filaments, especially at the 
edge of the cover glass; and, as he watched, he saw round and 
oval granular bodies appear in the filaments. He realized that they 
were spores, similar to those described by Ferdinand Cohn in 
other bacteria; and he recognized that Ms cultures underwent a 
cycle including every stage, from Davaine's motionless rod to 
the fully formed spore. He determined the optimal thermal con- 
ditions for spore formation and saw that the spores could again 
grow into typical anthrax rods. Recognizing that the spores were 
highly resistant to injurious influences, he grasped at once the 
significance of this property for the maintenance and spread of 
infection. He learned to differentiate true anthrax from the sep- 
ticemic disease which had confused the observation of BraueU, 


Leplat and Jaillard He further established that the hay bacillus 
(Bacillus siibtitis, commonly found in hay infusion), an organism 
very similar to Davaine's rod, and like it capable of producing 
spores, did aot cause anthrax when injected into animals. From 
all these facts he finally concluded that true anthrax was always 
induced by only one specific kind of bacillus and he formulated 
on the basis of this conclusion a number of prophylactic measures 
aimed at preventing the spread of the disease. 

One of Koch's e^eriments was of particular interest in proving 
the etiological role of Davaine's rods. He had sown fragments of 
infected tissues into drops of serum or of aqueous humor of the 
rabbit; and had allowed this primitive culture to incubate until 
the bacilM had multiplied to large numbers; then, from this first 
culture, he had inoculated a new drop of serum. After repeating 
the process eight times he found to his great satisfaction that the 
last culture injected into a susceptible healthy mouse was as 
capable of producing anthrax as blood taken directly from an 
animal just dead of the disease. Despite their thoroughness and 
elegance, these experiments still left a loophole for those who be- 
lieved that there was in the blood something besides the rods, 
capable of inducing anthrax. Although Koch had transferred his 
cultures eight times in succession, this was not sufficient to rule 
out the possibility that some hypothetical component of the blood 
had been carried over from the original drop and was responsible, 
instead of the bacteria, for transmitting the infection to the inocu- 
lated animal. It was this last debatable point that Pasteur's experi- 
ments were designed to settle. 

Pasteur knew from his earlier studies on spontaneous genera- 
tion that the blood of a healthy animal, taken aseptically during 
life, and added to any kind of nutrient fluid, would not putrefy or 
give rise to any living microorganism. He felt confident, there- 
fore, that the blood of an anthrax animal handled with aseptic 
precautions should give cultures containing only the anthrax 
bacillus. Experiment soon showed this to be die case, and showed 
also that rapid and abundant growth of the bacillus could be 
obtained by cultivating it in neutral urine; these cultures could 


be readily maintained through by trans- 

fers in the same medium. By adding one of to iffy 

cubic centimeters (nearly two ounces) of mine, then, 

after incubation and multiplication of the bacilli traosf eiring one 
drop of this culture into a new flask containing fifty cubic cen- 
timeters of urine, and repeating this process one hundred times 
in succession, Pasteur arrived at a culture in which the dilution 
of the original blood was so great of the order of 1 part in 
10CP that not even one molecule of it was left in the final 
material. Only the bacteria could escape the dilution, because 
they continued to multiply with each transfer. And yet, a drop 
of the hundredth culture Idled a guinea pig or a rabbit as 
rapidly as a drop of the original inf ected blood, thus demonstrat- 
ing that the "virulence principle** rested in the bacterium, or was 
produced by it 

Pasteur devised many other ingenious experiments to secure 
additional evidence of the etiological role of the anthrax bacillus. 
He filtered cultures through membranes fine enough to hold back 
the bacteria and showed that the clear filtrate injected into a 
rabbit did not make it sick. He allowed flasks of culture to rest 
undisturbed in places of low and constant temperature, until 
the bacteria had settled to the bottom; again the clear super- 
natant fluid was found incapable of establishing the disease in 
experimental animals, whereas a drop of the deposit, containing 
the bacterial bodies, killed them with anthrax. These results con- 
stituted the strangest possible evidence that the anthrax bacil- 
lus itself was responsible for the infection. However, Pasteur 
took care to point out that there still remained a possibility which 
had not been explored, namely that the bacilli produced a virus 
which remained associated with them throughout the culture, and 
which was the active infective agent. But even this hypothesis 
did not change the conclusion that the bacilli were living and 
were the cause of anthrax. The germ theory of disease was now 
firmly established. 


As as It became possible to grow the anthrax bacillus in 
pure culture, to identify it and to establish with it a reproducible 
disease in experimental animals, the way was open to elucidate 
many riddles that had baffled students of the problem during the 
preceding decades. 

Leplat and Jaillard had shown that rabbits inoculated with 
putrid anthrax blood died quickly without showing rods in their 
blood. Although Davaine had claimed that the disease so induced 
differed from true anthrax in length of the incubation period and 
in many other ways, he had not been able to prove his point. 
He clearly realized that the most convincing exposition of 
Leplat and JaiUard's error would be to discover the cause of the 
disease they had produced, but in this he had failed completely. 
It was in the blood that Davaine had originally seen the anthrax 
bacilli, and it was in the blood that he searched obstinately, and 
in vain, for the cause of the new disease. On the contrary, Pasteur, 
less bound by tradition and more resourceful as an investigator, 
soon discovered that Leplat and Jaillard's disease was associated 
with another type of bacillus present in immense numbers in 
many tissues but absent or rare in the blood. This bacillus has 
remained famous in all languages under the name of vibrion 
septique that Pasteur gave it. It was probably the vibrion septique 
that had been responsible for Paul Bert's results. The blood which 
he had treated with oxygen to loll the rods probably contained 
the mlmon septique, in the resistant spore stage, and thus was 
capable of causing a special disease in the inoculated animal. 

Pasteur found the new organism to be very common in nature, 
often present as a normal inhabitant of the intestinal canal, where 
it is harmless until certain circumstances allow it to pass through 
the intestinal barrier and into other organs. It invades the blood 
shortly after death and, as the disease which it causes has an 
extremely rapid course, it often kills animals infected with old 
anthrax blood before the anthrax bacillus itself has a chance to 
multiply. Thus were explained all the earlier observations in which 
animals receiving post-mortem blood from cases of anthrax died 
without exhibiting a trace of the rods originally seen by Davaine. 


Pasteur undertook a study of the 

and he recognized with surprise the bacillus 

of butyric acid fermentation discovered years before, the 

new organism was an obligate which could be cultivated 

only in the absence of air. With the assurance that practice 
had given Mm, he derived from fact important conclusions 
concerning the physiology of the "It is a ferment; 

and . . . forms carbon dioxide, hydrogen, and a amount of 

hydrogen sulfide which imparts an odor to the mixture. . . , 
When a post-mortem examination is made on an animal which 
has died o septicemia, we find tympanites, gas pockets in the 
cellular tissue of the groin or of the axilla, and frothy bubbles in 
the fluid which flows when an opening is made in the body. The 
animal exhales a characteristic odor toward the end of its life. Its 
parasites, driven out perhaps by this production of hydrogen 
sulfide, leave the skin, to take refuge at the extremity of its hairs. 
In short, septicemia may be termed a putrefaction of the living 

Except in a few prejudiced minds these studies on the anthrax 
bacillus and on the vibrion septique established the germ theory 
of disease, once and for all. The difficulties involved in separating 
the anthrax bacillus from the vibrion septique, and in disen- 
tangling the two distinct diseases that they cause, must be meas- 
ured by taking into account the lack of previous experience and 
the paucity of experimental techniques then available. This his- 
torical perspective helps in appreciating the intensity of the travail 
which preceded the birth of the new theory, and the convincing 
character of Koch's and Pasteu/s achievements. 

The causative agents of most other bacterial diseases were dis- 
covered and described within two decades after Koch's and Pas- 
teur's studies. It is worth remarking that this triumph, which 
looms so great in the history of medicine and has such import for 
the welfare of mankind, was to a large extent achieved through 
men of very ordinary talent The harvest comes abundantly, and 
often without much effort, to those who follow the pioneers, Dis~ 


covery of the causative agent and of the means of control of a 
given contagions disease constitutes, in reality, the last stage in 
centuries of unrecorded labor. It was necessary first for the dif- 
ferent diseases to be recognized and separated a process which 
required of the early clinicians prolonged observation and much 
judgment Then came the intellectual straggle of naturalists and 
chemists, who conceived the idea of the existence of micro- 
organisms and of the huge potential activities of those tiny forms. 
Natural philosophers, physicians, and epidemiologists had to 
have the creative imagination to foresee that the contagious be- 
havior of certain diseases could some day be explained in terms 
of the activity of minute living agents, traveling from patient to 
patient through many different channels. Then the experimenters 
had to establish that "spontaneous generation" does not occur, at 
least in the ordinary events of Me; and that microorganisms do 
come from parents similar to themselves. Finally before micro- 
biology could become a science, it had to be shown that microbial 
species are well-defined biological entities, and that each micro- 
organism exhibits dependable specificity in its action, be it as a 
ferment or as an agent of disease. 

In deciding which events were epoch-making in the develop- 
ment of the germ theory, medical scientists and historians of 
medicine focus attention on those achievements that have the 
most obvious bearing on the life of man. Thus, the isolation of 
the tubercle bacillus in 1882 is almost universally regarded as the 
high point in the unfolding of the science of medical bacteriology; 
but it is the importance of tuberculosis for man, even more than 
the distinction of the scientific discovery of its cause, which de- 
termines this judgment The earlier elucidation of the cause of 
anthrax, a disease of less importance than tuberculosis for man, is 
usually discussed in less enthusiastic terms. Bassf s demonstration 
as early as 1836 that a microscopic fungus was the agent of one of 
the silkworm diseases is dismissed in the form of a few statements. 
And no student of the history of infection ever mentions the early 
work done in the field of plant diseases, although all the great 
debates which presided at the birth of the germ theory of animal 


diseases were foreshadowed by the discussions on the causation 
of the epidemics of plant crops. 

Early in the nineteenth century, the fungus Clamceps purpurea 
was found to be the cause of ergot, a disease which blackens and 
elongates the kernels of rye in wet seasons. 

In 1813, Knight stated before the Horticultural Society in Lon- 
don that **Rust or mildew ... of wheat originates in a minute 
species of parasitical fungus which is propagated like other plants 
by seeds.** 

When, in 1845, the potato blight broke out on a disastrous scale 
in Europe, and in 1846 particularly in Ireland, it brought in its 
train sufferings and economic upheavals greater than those caused 
by most human diseases. Potato blight presents a special interest 
for the historian of the germ theory as many of the debates which 
enlivened animal pathology during the second half of the nine- 
teenth century had their counterpart a few decades earlier in the 
establishment of the causation of this disease of plants. 

Weather had been very unpleasant shortly before the blight 
broke out. For several weeks, the atmosphere had been one of 
continued gloom, with a succession of chilling rains and fog, the 
sun scarcely ever visible, the temperature several degrees below 
the average for the previous nineteen yars. The botanist, Dr. 
Lindley, held the theory that bad weather had caused the potato 
plants to become saturated with water. They had grown rapidly 
during the good weather; then when the fogs and the rain came, 
they absorbed moisture with avidity. As absence of sunshine had 
checked transpiration, the plants had been unable to get rid of 
their excess of water and in consequence had contracted a kind 
of dropsy. According to Lindley, putrefaction was the result of 
this physiological disease. The Reverend Berkeley, "A gentleman 
eminent above all other naturalists of the United Kingdom in his 
knowledge of the habits of fungi,** held a different theory and 
connected the potato disease with the prevalence of a species 
of mold on the affected tissues. To this, Lindley replied that 
Berkeley was attaching too much importance to a little growth 
of mold on the diseased potato plants. He added furthermore that 


**as soon as living matter lost Its force, as soon as diminishing 
vitality took the place of the customary vigour, all sorts of para- 
would acquire power and contend for its destruction. It was 
so with all plants, and aU animals, even man himself. First came 
feebleness, next incipient decay, then sprang up myriads of crea- 
tures whose life could only be maintained by the decomposing 
bodies of their neighbours. Cold and wet, acting upon the potato 
when it was enervated by excessive and sudden growth, would 
cause a rapid diminution of vitality; portions would die and decay, 
and so prepare the field in which mouldiness could establish 
itself" 2 

Thus, the professional plant pathologists, represented by the 
learned Dr. Lindley, believed that the fungus (Botrytis infestans) 
could become established on the potato plant only after the latter 
had been debilitated by unhealthy conditions, whereas the Rev- 
erend Berkeley, while not ignoring the influence of bad weather, 
saw the fungus as the primary cause of the disease with fog and 
min as circumstances which only favored its spread and growth. 
In this manner the controversies which were to bring Pasteur face 
to face with the official world of the French Academy of Medicine 
were rehearsed in the Gardener's Chronicle, over the dead body 
of a potato invaded by the fungus Botrytis infestans. This hap- 
pened thirty years before the beginnings of bacteriological times 
as recorded in medical histories. 

The two decades which followed the work of Koch and Pasteur 
on anthrax, and which saw the discovery of so many agents of 
disease, have been called the golden era of bacteriology. But they 
were in reality only an era of exploitation during which a host 
of competent but often uninspired workers applied to the prob- 
lems of contagion the techniques and intellectual approach which 
had reached maturity in the persons of Pasteur and Koch, after 
two centuries of scientific efforts. 

2 Quoted by E. D. Large in The Advance of the Fungi. (London: 
Jonatkm Cape, 1940.) 


Many of the bacterial of discovered by the 

German of bacteriology. was due In to the 

mastery by Koch and his of the In the 

isolation and identification of microbial cultures. Even im- 

portant was the fact that, under the rofiuence of 

Pasteur, the French school, numerically far com- 

pletely organized,, became chiefly concerned with another aspect 
of the study of infectious disease, namely the problem of im- 
munity. One should not assume, however, that Pasteur had be- 
come indifferent to the etiological problems of infection. Although 
he did not pursue systematically the isolation of pathogenic 
agents, he contributed to this field many observations that reveal 
his pioneering mentality. 

The causative agents of anthrax, chicken cholera and swine 
erysipelas were, until 18S4 ? the microorganisms most extensively 
used by Pasteur for Ms investigations on immunity. In addition, 
he found time in the midst of all his studies to visit hospital wards 
and morgues, where he would arrive accompanied by Roux and 
Chamberland, carrying culture flasks and sterile pipettes. With 
precaution that appeared meaningless even to many enlightened 
physicians of the time, he would take samples of pathological 
material for microscopical and bacteriological study. 

^Childbirth" or "puerperal" fever was then causing immense 
numbers of deaths in maternity wards. Despite the visionary teach- 
ings of Semmelweis in Vienna, and of Oliver Wendell Holmes 
in Boston, physicians did not regard the disease as contagious, 
but rather explained it in terms of some mysterious metabolic 
disorder. Pasteur had observed in the uterus, in the peritoneal 
cavity and in blood clots of diseased women a microorganism 
occurring "in rounded granules arranged in the form of chains or 
string of beads," and he became convinced that it was the most 
frequent cause of infection among women in confinement. 

In March 1879 there took place in the Paris Academy of Medi- 
cine a discussion on the cause of puerperal fever, One of the 
academicians, Hervieux, had engaged in an eloquent discourse, 


during which he spoke in sneering terms of the role of micro- 
organisms in disease; as we have shown, in 1879 the germ theory 
was not yet universally accepted in medical circles. Hervieux had 
contrasted the true C4 miasm or puerperal fever" with "those micro- 
organisms which are widely distributed in nature, and which, 
after all, appear fairly inoffensive, since we constantly live in 
their midst without being thereby disturbed." 

Irritated by the vague reference to the "puerperal miasm, 9 * Pas- 
teur interrupted the speaker from his place in the audience and 
retorted with vigor: **The cause of the epidemic is nothing of the 
Mndf It is the doctor and his staff who carry the microbe from a 
sick woman to a healthy woman!" And when Hervieux retorted 
that he was convinced that no one would ever find this microbe, 
Pasteur darted to the blackboard replying, "There it is," and he 
drew the organisms "shaped Hke strings of beads" which are now 
so wel known under the name of "streptococcus." 

Every occasion was for Pasteur a pretext for microscopic study. 
Uninformed as he was of medical problems, he had the genius to 
make observations and establish correlations which, unorthodox 
at the time, have been vindicated by subsequent developments. 
Illustrative of his keen judgment of the role of microorganisms in 
the pathogenesis of disease is the case of the relation of staphylo- 
coccus to bone infections. The story has been told by his assistant 
Duclaux. "I was then suffering from a series of boils. The first 
thing that Pasteur did when I showed him one of them was to 
prick it, or rather have it pricked, for he was not fond of operating 
himself, and to take therefrom a drop of blood in order to make a 
culture, an undertaking in which he was successful. A second boil 
gave the same result, and thus the staphylococcus was discovered, 
so well known since that time. He found the same microbe, made 
up of little agglomerated granules, in the pus of an infectious 
osteomyelitis which M. Lannelongue had submitted to him for 
examination. With a fine audacity, he declared immediately that 
osteomyelitis and boils are two forms of one and the same disease, 
and that the osteomyelitis ... is the boil of the bone. What 
could be bolder than to liken a grave disease taking place in the 


depths of the to a To 

confound and When he 

opinion before the Academy of Medicine, I picture to myself the 
physicians and surgeons present at the meeting, staring at him 
over their spectacles with suiprise and uneasiness. Nevertheless, 
he was right s and this assertion, daring at the time, was a first 
victory of the laboratory over the clinic." 

In these examples of his mode of attack on medical problems, 
we see Pasteur applying the methods which were then rapidly 
becoming standard practice in the bacteriological laboratories of 
Europe, Of greater interest to illustrate the pioneering and ad- 
venturous quality of his genius are the discoveries that he made 
toward the end of his scientific life, in attempting to bring rabies 
within the scope of the germ theory of disease. 

Rabies was then known as a disease contracted by man or a 
few species of large animals from the bite of rabid dogs or wolves. 
In the hope of discovering the causative microorganism Pasteur 
collected saliva from an infected child and injected it into a 
rabbit. In agreement with his expectations, he produced a fatal 
disease, readily transmissible from rabbit to rabbit* For a short 
time, he held the belief that he had discovered the cause of rabies 
and described the organism he had isolated in words which show 
his skill and care in reporting those morphological characteristics 
that he considered of special interest It is an extremely short 
rod, someivhat constricted in its center, in other words shaped 
like an 8 ... Each one of these small microorganisms is sur- 
rounded, as can be detected by proper focusing of the micro- 
scope, with a sort of aureola that really seems to belong to it ... 
it appears that the aureola consists of a mucous substance . . ." 
The trained bacteriologist will have no difficulty in recognizing 
the pneumococcus in this accurate description. 

Pasteur soon realized, however, that the microorganisms with 
an aureola isolated from the saliva of the rabid child could also 
be found in the saliva of normal individuals, and was often absent 
in other persons suffering from rabies, Moreover, the disease 
which it caused in rabbits was different from true rabies. It was 


not the microorganism that he had been looking for, and he 
turned immediately to other techniques for the solution of his 

Bacteriological studies which must have been very disheart- 
ening failed to reveal the cause of rabies. Attempts were made 
to cultivate a microorganism in spinal fluid, and even in fresh 
nerve substance obtained from normal animals, but all in vain. 
This failure is not surprising, for it is now known that rabies is 
caused by a filterable virus, which cannot be seen by ordinary 
microscopy, and which has not yet been cultivated in lifeless bac- 
teriological media. With an uncommon and truly admirable in- 
tellectual agIity > Pasteur then gave up the in vitro cultural tech- 
niques, to the development of which he had contributed so much. 
Heretofore, he had emphasized the necessity of discovering for 
each type of microorganism the nutrient medium most selectively 
adapted to its cultivation. He now conceived the idea of using the 
susceptible tissues of experimental animals, instead of sterile nu- 
trient solutions, to cultivate the virus of the disease; the concept 
of selectivity of cultural conditions was thus simply carried over 
from lifeless media to receptive living cells. 

The general symptoms of rabies suggested that the nervous 
system was attacked during the disease. Indeed, there had been 
published experiments showing that the infective matter of rabies 
was present not only in the saliva, but also in the nerve substance 
of mad animals. On the other hand, infected nerve tissue inserted 
under the skin of an animal was known to be able to induce 
rabies. Unfortunately this method of transmission was as uncer- 
tain and capricious as transmission through the saliva; rabies did 
not always appear, and when it did, it was often after a prolonged 
incubation of several months. Inoculation under the skin, there- 
fore, was ill adapted to the designing of convincing experiments. 
Someone in the laboratory (probably Roux) suggested depositing 
the virus in the nerve centers; the proof of its presence and de- 
velopment would then be the appearance of rabies in the inocu- 
lated animal. Nerve tissue seemed to be an ideal medium for the 
virus of rabies, and to fulfill naturally for it the condition of selec- 


tivity which was the of the As the 

main problem was to access to under con- 

ditions, the surest way was to to dogs under 

the dura mater, by trephining. Roux, who a part in 

this phase of the work, has left the following account of the cir- 
cumstances under which the operation was introduced in Pas- 
teur's laboratory: "Ordinarily an experiment once conceived and 
talked over was carried out without delay. This one, on which 
we counted so much, was not begun immediately, for Pasteur 
felt a veritable repugnance toward vivisection. He was present 
without too much squeamishness at simple operations, such as a 
subcutaneous inoculation., and yet, if the animal cried a litde, he 
immediately felt pity and lavished on the victim consolation and 
encouragement which would have been comical had it not been 
touching. The thought that the skull of a dog was to be perfo- 
rated was disagreeable to him; he desired intensely that the ex- 
periment be made, but he dreaded to see it undertaken. I per- 
formed it one day in his absence; the next day, when I told him 
that the intracranial inoculation presented no difficulty,, he was 
moved with pity for the dog: *Poor beast. Its brain is certainly 
badly wounded. It must be paralyzed.' Without replying, I went 
below to look for the animal and had him brought into the labo- 
ratory. Pasteur did not love dogs; but when he saw this one full 
of Me, curiously ferreting about everywhere, he showed the great- 
est satisfaction and straightaway lavished upon him the kindest 
words. He felt an infinite liking for this dog which had endured 
trephining without complaint and had thus relieved him of 
scruples concerning the operation." 

The dog inoculated by trephination developed rabies in four- 
teen days and all the dogs treated in the same fashion behaved in 
a similar manner. Now that the cultivation of the virus in the ani- 
mal body was possible the work could progress at a rapid pace, 
as in the case of anthrax, fowl cholera and swine erysipelas, 

Thus was discovered a technique for the cultivation of an un- 
known infectious agent in the receptive tissues of a susceptible 
animal. This technique has permitted the study of those agents 


of disease which are not cultivable in lifeless media, and has 
brought them within the fold of the germ theory of disease. The 
Henle-Koch postulates in their original form could not be applied 
to the study of filtrable viruses and it is one of the most telling 
examples of Pasteur's genius that he did not hesitate to free him- 
self of their requirements as soon as they proved unadapted to 
the solution of his problem. For Mm, doctrines and techniques 
were tools to be used only as long as they lent themselves to the 
formulation and performance of meaningful experiments. 

The demonstration that invisible viruses could be handled al- 
most as readily as cultivable bacteria was a great technical feat, 
and its theoretical and practical consequences have been immense. 
Even more impressive, perhaps, is the spectacle of Pasteur, then 
almost sixty years of age and semiparalyzed, attacking with un- 
diminished vigor and energy a technical problem for which his 
previous experience had not prepared him. Throughout his life 
the concept of selectivity of chemical and biological reactions had 
served him as the master key to open the doors through which 
were revealed many of nature's secrets. From the separation of 
left- and right-handed crystals of tartaric acid by selective pro- 
cedures or agents, through the cultivation of yeast and of lactic, 
acetic and butyric bacteria in chemically defined media, to 
the differentiation of the anthrax bacillus from the vibrion sep- 
tique by cultivation in vitro, and by infection of experimental 
animals, he had in the course of twenty-five years applied the 
concept of selectivity to many different situations. The propaga- 
tion of the rabies virus in receptive nervous tissue demonstrated 
that, if used with imagination, the same concept was applicable 
to still other biological problems. In his hands, the experimental 
method was not a set of recipes, but a living philosophy adaptable 
to the ever-changing circumstances of natural phenomena. 


Mechanisms of Contagion and Disease 

So, naturalists observe, a fiea 

Has smaller fleas that on him prey; 

And tliese have smaller still to bite *em; 

And so proceed ad infinitum. 


THE DEMONSTRATED!? that mlcrobial agents can be the primary 
cause of disease left unanswered most of the questions relevant 
to the mechanisms by which contagion spreads from one Indi- 
vidual to another, and by which it manifests itself in the form of 
characteristic symptoms and pathological alterations. Countless 
species of microorganisms swarm in the air that we breathe, the 
foods and fluids that we ingest, the objects that we touch. And 
yet, few of them become established and multiply in the bodies 
of plants, animals and man; still fewer are able to cause disease. 
How do the disease-producing species differ from their innocuous 
relatives? What weapons do they possess which give them the 
power to inflict on the invaded host injury more or less profound, 
symptoms more or less distressing? Why do so many individuals, 
in plant and animal as well as in human populations, remain ap- 
parently unaffected in the course of an epidemic, although they 
are as fully exposed as their stricken brothers? The course of epi- 
demics is sometimes predictable, more often capricious, never 
explicable in the simple terms of the mere presence or absence 
of the causative microorganism. Whence do epidemics originate? 
What factors determine their growth and their decline, both in 
space and in time? Why do they subside, as mysteriously and 
often as abruptly as they began? 


These questions may appear abstract and even meaningless to 
the citizen of a well-policed community, living in a state of peace 
and economic well-being. However, they have frightening signifi- 
cance for those populations which are victims of the upheavals of 
war or of social disasters; three decades ago, they were made part 
of universal consciousness by the impact of the influenza epidemic 
in 1918-1919. 

Before the twentieth century, the riddle of contagion was ever 
present in the mind of man; the threat of infection and of epi- 
demics introduced a constant element of mystery and terror in 
the life of the individual and of society. For example, cholera a 
disease practically unknown today in the Western world made 
several devastating incursions in Europe during Pasteur's life- 

For the modem man, cholera is a disease of the East. It suggests 
the Mohammedan pilgrimages to and from Mecca, and the pol- 
luted rivers of Hindustan. Often traveling as a silent member of 
the caravans, it may suddenly become raging, decimate its fellow 
travelers, then again quiet down and become, as before, unnotice- 
able. In the villages as well as in the crowded cities of Asia, along 
the rivers and caravan trails, cholera appears unexpectedly in a 
few isolated victims, spreads rapidly through the communities, 
reaches its maximum in a few weeks, killing half of the persons 
whom it strikes, then declines to a few sporadic cases before dis- 
appearing as mysteriously as it came, for an unpredictable length 
of time. So much terror and so much mystery in a name! 

There had been well-identified cases of cholera in Europe be- 
fore the nineteenth century, in Nimes in 1654, in London in 1669 
and 1676, in Vienna in 1786. However, the epidemics which oc- 
curred after 1817 differed markedly in their "dispersiveness" from 
these isolated outbreaks. In the wet season of May 1817, cholera 
appeared in the northern provinces of Bengal, this time affecting 
not only the untouchables, but other castes and even Europeans. 
It spread ultimately over almost all India and from there began 
a world-wide dissemination that reached Russian cities after six 
years. Another wave of cholera, also coining from India, struck 


Russia in and in 1831. Thus, the Bret 

pandemic occurred in two parts, 1817 to 1325, when the 

borders of Europe were reached, the 1828 to 1838, 

when the spread over most of Western Europe* The 

came in 1838 unexpectedly; no knew the of the epi- 

demic or the reason for its sudden termination. 

The second pandemic, like the first, came from India. It began 
around 1840, reached Europe in 1847, remained there some twelve 
years and again petered out mysteriously. It was during this pan- 
demic that John Snow established the connection of the disease 
with contaminated water,, tracing the London outbreak of 1854 
to a particular well in Broad Street. He ascertained that a cess- 
pool drained into this well, and that there had been a case of 
cholera in the house served by the cesspool. 

A third pandemic became manifest in Europe around 1885; 
after a very irregular course, during which Russia, Austria and 
Germany were affected, it came to an end in 1875. Despite Snow's 
discovery, the cause of the disease was still mysterious, as is il- 
lustrated by the episode reported on page 241, during which 
Pasteur, Claude Bernard and Sainte-Claire Deville made their 
futile attempts at analyzing the gases of the air in the cholera 
wards of Paris. 

The fourth pandemic began in 1881. Traveling with the Moslem 
pilgrims to Mecca, it reached Egypt in 1883 and Southern France, 
Italy and Spain in 1884; in this last country alone the disease 
caused 57 7 GOO deaths out of 160,000 cases during 1885. In 1883 a 
French mission including Pasteur's assistants, Roux, Nocard, and 
Thuillier, and a German mission under the leadership of the 
great Robert Koch himself arrived in Egypt to investigate the 
cause of the disease. The epidemic, however, had almost run its 
course by the time the two commissions began their studies. One 
of the last sporadic cases was that of Thuillier, who by a cruel 
irony of fate died in Alexandria of the most violent form of 
cholera. The French mission returned home while the German 
group proceeded to Calcutta, where the epidemic was still raging. 
There* in December 1883, Koch isolated the cholera bacillus. The 


microblal cause of the disease was thus Identified, but the mystery 
of its capricious course was not solved thereby. Cholera once more 
invaded Europe shortly after Koch's discovery, causing 8605 
deaths out of 17,000 cases during an outbreak in Hamburg from 
August to November 1892. An epidemic of large proportions also 
occurred in Russia in 1907-1919. 

The many theories that have been evolved to account for the 
explosive and erratic behavior of cholera epidemics are of interest 
only in illuminating the length to which imagination will go in 
order to satisfy the human urge for explaining natural events, 
even when the essential knowledge is still lacking. It is generally 
held at the present time that man constitutes the reservoir from 
which new infections are initiated, a view based upon the fact 
first recognized by Koch that certain individuals who do not 
show any symptoms of the disease can carry the cholera bacilli 
and transmit them to susceptible persons. The bacilli harbored 
by these apparently healthy ^carriers' 7 are assumed to be capable 
of initiating widespread epidemics when other conditions still 
shrouded in mystery are satisfied. To many hygienists and stu- 
dents of public health, it is precisely the understanding of this 
"epidemic climate" which constitutes the real problem, the riddle 
of contagion, and they regard this unsolved problem as more im- 
portant than the mere discovery of some new bacillus in explain- 
ing the spread of infection. This attitude is symbolized by the 
picturesque career of the great German hygienist, Max von 
Pettenkofer, who opposed a "soil theory" of cholera to the purely 
bacteriological theory of his rival Robert Koch. 

Like Pasteur, Pettenkofer had been trained as a chemist. At first 
very active in the field of analytical chemistry, then of medicinal 
chemistry, he had become more and more concerned with the ap- 
plications of chemical knowledge to physiology and pathology, 
and more especially to hygiene and public health. Nevertheless, 
he retained for a long time a lively interest in all aspects of chem- 
istry. For example in 1863, precisely during the period when Pas- 
teur was lecturing to the students of the Paris School of Fine 
Arts on the chemical basis of oil painting, Pettenkofer undertook 


a study of the oils, pigments and varnish used by the old masters, 
in order to determine the cause of the alarming alterations which 
were then threatening the paintings in the galleries of Munich. 
However, it is as the high priest of hygiene that Pettenkofer won 
the admiration and love of the world, and particularly of his 
fellow citizens in Munich. He regarded hygiene as an all-embrac- 
ing philosophy of life, concerned not only with an abundant sup- 
ply of clean water and air, but also with trees and flowers because 
they contributed to the well-being of men by satisfying their 
aesthetic longings. Although microorganisms played only a small 
part in his philosophy of public health, he persuaded the Munich 
city fathers to have clean water brought in abundance from the 
mountains to all houses, and to have the city sewage diluted 
downstream in the Isar, all in the name of salubrity and aesthetic 
hygiene. With these steps, the great cleaning-up of Munich began. 
The mortality of typhoid fell from 72 per 1,000,000 in 1880 to 14 in 
1898. Munich thus became one of the healthiest of European 
cities, thanks to the efforts of this energetic and public-minded 
citizen who was entirely unimpressed by the germ theory of 

As years went on, Pettenkofer devoted more and more atten- 
tion to the epidemiology o cholera, and taught that certain 
changes in the soil were of primary importance in establishing 
an "epidemic climate." While admitting that the disease had a 
certain specific cause, a materies morbi, he emphasized the im- 
portance of local, seasonal, and individual conditions which had 
to be satisfied before the infection could occur. After 1883, he 
admitted that the Koch bacillus was the specific cause of cholera 
but retained his conviction that the new discovery had not solved 
the problem, and that the bacillus alone could not produce the 

So convinced was he that he resolved to prove his thesis by 
ingesting cholera bacilli. He obtained a culture freshly isolated 
from a fatal case of the epidemic then raging in Hamburg and, 
on October 7, 1892, swallowed a large amount of it on an empty 
stomach, the acidity of which had been neutralized by drinking 


an adequate quantity of sodium carbonate; these were the very 
conditions stated by Koch as most favorable for the establishment 
of the disease. The number of bacilli ingested by Pettenkofer 
was immensely greater than that taken under normal conditions 
of exposure, and yet no symptoms resulted except a 'light diar- 
rhea/* although an enormous proliferation of the bacilli could be 
detected in the stools. Shortly thereafter, several of Pettenkofer's 
foEowers, including Emmerich and Metchnikoff, both of whom 
were soon to become important investigators in bacteriological 
science,, repeated the experiment on themselves with the same 
result. None of them doubted that the bacillus discovered by Koch 
was the cause of cholera. The experiment merely demonstrated 
that infectious diseases and epidemics are complex phenomena 
involving, in addition to the infective microorganisms, the physio- 
logical state of the patient, the climate and the environment, the 
social structure of the community, and countless other unsus- 
pected factors. The implantation of bacilli, like the planting of 
seed, does not necessarily insure a growth. 

Pasteur had come into contact with the complexities of the 
problem of infection during his studies on silkworms. He knew 
that the discovery of the microbial agent of a disease was only 
one link in the solution of the riddle and that, as a mere isolated 
fact, it was of little use to the physician, and of limited intellec- 
tual interest. These reasons probably played an important part in 
his decision to devote his energy to the elucidation of the mecha- 
nisms by which microorganisms can cause disease and by which 
they are carried from one individual to another. This type of pre- 
occupation may account for the subjects which he selected for his 
studies. Anthrax, chicken cholera, swine erysipelas, were not the 
most important or most dramatic subjects from the viewpoint of 
man's immediate interests, but they lent themselves to experimen- 
tation better than human diseases. 

Pasteur's first papers on animal pathology are replete with ob- 
servations and theories which indicate that, intellectually, he was 
chiefly concerned with the mechanism of the reactions between 


parasite and infected host. As he was beginning to work on this 
problem, however, Ms experiments on chicken cholera unexpect- 
edly revealed the possibility of vaccinating against infectious dis- 
eases. Immediately, the prospect of this development took prece- 
dence over his other scientific interests and from then on he 
directed all his experimental work to the problem of vaccination. 
Twenty years earlier, he had abandoned theoretical studies on 
the mechanisms of fermentation to deal with the practical prob- 
lems involved in the manufacture of wine and vinegar; he was 
young then, and life permitted him to come back after 1871 to 
the speculations of his early years, and to formulate in more defi- 
nite terms the nature of the fermentation process which he had 
envisioned in 1861. When he discovered vaccination, in 1882, he 
was sixty years old, and Bad only six years of active work left 
before disease struck him again. The labors and struggles of this 
last phase of his scientific life never gave him the opportunity 
of returning to the epidemiological problems and to the mecha- 
nisms of toxemia, which appear as sketchy visionary statements 
in the notes that he published between 1877 and 1882. Histo- 
rians of bacteriology have neglected this aspect of Pasteur's work. 
It is very probable, however, that, had not circumstances chan- 
neled his efforts into the dazzling problems of vaccination, the 
study of the physiological and biochemical aspects of infection 
might have yielded results which now remain for coming genera- 
tions to harvest 

The shepherds of the Beauce country had noticed that sheep 
allowed to graze on certain pastures were likely to contract 
anthrax, even after the fields had been abandoned for years, as 
if a curse had been placed on them. In the center of France cer- 
tain "dangerous mountains" were also known to farmers as being 
unfit to pasture their animals for the same reason. The existence 
of these anthrax fields had been the source of many objections 
to the view that the rods occurring in the blood of sick animals 
were the cause of the disease. Why should the spread of the con- 
tagion from one animal to the other be limited to certain pastures, 


to these "accursed fields* 7 or "dangerous mountains"? If the con- 
tagion were due to the transmission of the anthrax rods by direct 
contact between animals, or through the air, or by the inter- 
mediary of flies, as Davaine believed, why should these agencies 
of transmission be restricted by the hedges or stone walls en- 
closing particular fields? Davaine had no answer to these embar- 
rassing questions. 

The discovery by Koch that anthrax bacilli produce resting 
forms, the spores, which can survive for prolonged periods of time 
without losing their ability to produce disease, made it likely that 
these spores might often behave as agents of transmission. Pas- 
teur was prepared for this theory by his earlier experience in the 
silkworm nurseries. There, he had seen the spores of the flacherie 
germs survive at least a year and germinate again in the nur- 
series the following spring. Turning his attention to anthrax, he 
first established in the laboratory that sheep fed on fodder ar- 
tificially contaminated with anthrax spores developed the symp- 
toms and lesions of the natural disease; then he set himself the 
task of elucidating how animals became infected under field con- 

It was first necessary to determine whether anthrax spores 
really existed in the "accursed fields." In the Beauce country, the 
shepherds were in the habit of burying the animals right in the 
fields where they had died. Although one could reasonably as- 
sume that the anthrax rods or their spores were present for a 
time in the pit, it was not an easy task to demonstrate that they 
actually survived in the soil, where everything else undergoes 
decomposition. The demonstration was achieved by suspending 
suspected soil in water, letting it settle, collecting the fine par- 
ticles and then heating them at 80 C. to kill any vegetative bac- 
terial forms. When the heated material was injected into guinea 
pigs, several of them died of anthrax, thus demonstrating that the 
spores were capable of surviving in the soil. In fact, living spores 
could be found in soil near pits in which animals had been buried 
twelve years before. 

How could sheep come into contact with the spores buried in 


the ground with the dead animals? The spores have no motility 
and cannot by themselves reach either the surface of the soil or 
the plants ingested by the animals. Pasteur guessed that earth- 
worms might bring spores up from the lower layers, and he 
proved Ms hypothesis by collecting worms from the soil over a 
burial pit containing infective remains. Moreover, he noticed an 
interesting correlation between the geology of a region and the 
prevalence there of anthrax in farm animals; for example, the 
disease was unknown where the topsoil was thin and sandy, or in 
the chalky soil of the Champagne country where the conditions 
are not favorable for the life of earthworms. 

Another puzzling fact found its ready explanation in terms of 
the germ theory. It had long been known that mortality was the 
highest where animals grazed on the fields after the harvest of 
cereal crops. Pasteur recognized that the dried stubble and chaff 
left standing in the fields often inflicted upon the animals 
superficial wounds which, unimportant by themselves, gave the 
anthrax spores a chance to become established in the body and 
to initiate infection. He was very proud of this discovery and 
often referred to it Although of small practical importance, it 
was probably for him a symbol of all the subtle factors, usually 
undetected, which control the manifestations of the germ theory 
of disease and conceal its operations to the unprepared mind. 

These facts, so obvious once they had been recognized, led to 
the formulation of simple rules for the prophylaxis of anthrax. 
Pasteur never tired of advising the farmers not to abandon the 
dead animals in the pastures, but to destroy them by burning or 
by burying them in special grounds where sheep and cattle would 
not be allowed to graze. 

Most of the early investigations on anthrax were carried out in 
the farms of the Beauce country for Pasteur, so often accused by 
his medical opponents of being merely a laboratory scientist," 
was always ready to move into the field when the work de- 
manded it. Roux has described the intimate contact between 
the laboratory and the farms during the anthrax campaign: 

"For several years in succession, at the end of July, the labora- 


tory of the Rue dTJlm was abandoned for Chartres. Chamberland 
and I settled there with a young veterinarian, M. Vinsot. . . . 
Pasteur came every week to give the directives for the work. 
What pleasant memories we have kept of the campaign against 
anthrax in the Chartres country! Early in the morning, there were 
visits to the flocks of sheep scattered over all the vast Beauce 
plateau glimmering under the August sun; post-mortem examina- 
tions were performed at the slaughterhouse of Sours, or in the 
farmyards. The afternoon was devoted to bringing the notebooks 
up to date, writing to Pasteur, and getting ready for the new 
experiments. The days were rich in activity, and how interesting 
and healthy was this bacteriology in the open air! 

**On the days when Pasteur came to Chartres, the lunch at the 
Hotel de France did not last long, and we immediately proceeded 
by carriage to Saint-Germain, where M. Maunoury had placed 
his farm and his herds at our disposal. We discussed during the 
trip the experiments of the preceding week and the new ones to 
be undertaken. Upon arrival, Pasteur would hasten to the sheep 
parks. Motionless near the gates, he would observe the experi- 
mental animals with that sustained attention from which nothing 
could escape; for hours in succession, he would keep his gaze 
fastened on a sheep that he thought diseased. We had to remind 
him of the hour and show him that the spires of the Chartres 
cathedral were beginning to fade into the night before he could 
make up his mind to leave. He would question farmers and help- 
ers, and listened in particular to the opinions of shepherds who, 
on account of their solitary life, devote all their attention to the 
herds and often become acute observers. 

"No fact appeared insignificant to Pasteur; he knew how to 
draw the most unexpected leads from the smallest detail. The 
original idea of the role of earthworms in the dissemination of 
anthrax was thus born one day when we were walking through 
a field in the farm of Saint-Germain. The harvest was in and there 
remained only the stubble. Pasteur's attention was drawn to a 
part of the field where the earth was of different color; M. Mau- 
noury explained that sheep dead of anthrax had been buried there 


the preceding year. Pasteur, who always observed things at close 
range, noticed at the surface a multitude of those small casts of 
soil such as are ejected by earthworms. He then conceived the 
idea that in their endless trips from the lower levels, the worms 
bring up the anthrax spores present in the earth, rich in humus, 
that surrounds the cadavers. Pasteur never stopped at ideas, but 
immediately proceeded to the experiment. . . . The earth ex- 
tracted from the intestine of one of the worms, injected into 
guinea pigs, forthwith gave them anthrax/' 

It was during the same period that Darwin on his country 
estate also became interested in earthworms and came to look 
upon them as the silent but effective toilers of the soil, a view 
which he developed in his book Formation of Vegetable Mould, 
through the Action of Worms, with Observations on Their Habits. 
There is an atmosphere of idyllic and pastoral poetry in the pic- 
ture of these two scientist-philosophers, the one combating dis- 
ease and the other formulating the concept of evolution, both 
discovering natural laws while observing earthworms in the 
shadows of Gothic cathedrals. 

Pasteur began in 1878 the study of chicken cholera, a disease 
that despite its name bears no relation to human cholera. The 
course of chicken cholera differs profoundly from that of anthrax. 
When an epidemic attacks a barnyard, it spreads through it with 
extreme rapidity, killing most of the birds within a few days. 
Normal chickens injected with pure cultures of the chicken 
cholera bacillus always die within forty-eight hours, often in less 
than twenty-four. The mere feeding of contaminated food or 
excrements is sufficient to establish a disease with a course almost 
as rapidly fatal. Rabbits are equally susceptible, and, like 
chickens, uniformly contract the infection when exposed to the 
chicken cholera bacillus. 

In contrast with chickens and rabbits, adult guinea pigs exhibit 
a peculiar resistance to the infection. These animals develop an 
abscess which remains localized and which may persist for pro- 
longed periods of time before it opens and heals spontaneously. 


without at any time disturbing the general health and appetite 
of the animal. This slow and retrogressive course of the infection 
in the guinea pig is not due to a change in the virulence of the 
bacillus, for chickens and rabbits die of the acute form of the 
disease when inoculated with a minute amount of the abscess 
material, Pasteur immediately saw the implications of these facts 
for the problem of epidemiology: 

"Chickens or rabbits living in contact with a guinea pig suf- 
fering from such abscesses might suddenly become sick without 
any apparent change in the health of the guinea pig itself. It 
would be sufficient that the abscesses open and spread some of 
their contents onto the food of the chickens or rabbits. Anyone 
observing these facts and ignorant of the relationship that I have 
just described would be astounded to see the chickens and rabbits 
decimated without any apparent cause, and might conclude that 
the disease is spontaneous. . . . How many mysteries pertaining 
to contagion might some day be explained in such simple terms!" 

Three years later, while studying swine erysipelas in the South 
of France, Pasteur made an observation which revealed that this 
epidemic disease was caused by a microorganism pathogenic not 
only for swine, but also for other animal life. 

"Shortly after our arrival in the Vaucluse, in November 1882, 
we were struck by the fact that the raising of rabbits and pigeons 
was much neglected in this district because these two species 
were, at frequent intervals, subject to destructive epidemics. Al- 
though no one had thought of connecting this fact with swine ery- 
sipelas . . . experiments soon showed that rabbits and pigeons 
died of a disease caused by the erysipelas microorganism." 

Thus, it became obvious that one animal species could serve 
as a reservoir of infection for another species, or even for man. 
The subsequent development of epidemiology was to provide 
many examples of the fact that wild and domesticated animals 
can act as natural reservoirs of certain infectious agents: the part 
played by rodents in the dissemination of plague and typhus, by 
rabbits in the infection of man with tularemia, by monkeys in the 
maintenance of yellow fever in the South American jungle, by 


domesticated birds in the spread of parrot fever, by the vampire 
bat in the transmission of rabies to man and to large animals, are 
examples which illustrate the importance of the animal reservoir 
problem in the transmission of disease. 

The fact that certain ostensibly healthy individuals harbor in- 
fective microorganisms is also of great importance in maintaining 
a constant source of infection. After recovery from a disease, mild 
or severe, men or animals often continue to carry the causative 
agent and can transmit it to susceptible individuals. Chicken 
cholera revealed to Pasteur the existence of this "carrier" state. 
He observed that a few birds now and then resisted the epidemic 
and survived for prolonged periods, constantly releasing the viru- 
lent bacilli in their excreta. Moreover, certain chickens which ap- 
peared extremely resistant, and did not exhibit any general symp- 
toms of disease, showed on the surface of their body a persistent 
abscess containing large numbers of virulent bacilli Like the 
guinea pigs mentioned above, these birds were carriers of the 
infective agent and they constituted a constant reservoir of infec- 

There is overwhelming evidence that the "carrier state" is of 
paramount importance in determining the initiation of new out- 
breaks. The notorious "typhoid Mary" was a cook who, through- 
out her life, remained a carrier of typhoid bacilli and unwittingly 
brought about outbreaks of the disease among those with whom 
she associated. Carriers of diphtheria bacilli, of virulent strep- 
tococci, and of many other infectious agents are a constant source 
of danger in exposed communities, and of concern for the public 
health officer. As mentioned earlier in this chapter, the carrier 
state doubtless plays an important part in the initiation of epi- 
demics of Asiatic cholera, and Pasteur's prophetic observations 
on the animal reservoirs of swine erysipelas and of chicken 
cholera provide a pattern according to which many obscure facts 
of epidemiology find at least a partial explanation. 

The germ theory of fermentation and of disease was based on 
a belief in the specificity and permanence of the biological and 


chemical characteristics of microbial species. Under the influence 
of Colin and Koch, this concept of specificity became a rigid doc- 
trine; each microorganism was claimed to be unchangeable in its 
form and properties, and to remain identical with its precursors 
under all circumstances. Pasteur first recognized that this con- 
cept had to be somewhat modified during the course of his studies 
on fermentation. As will be remembered, he had observed that 
the mold Mucor mucedo, which grew in a filamentous form in 
the presence of air, became yeasdike and behaved as an "alco- 
holic ferment" under anaerobic conditions. The mold returned 
immediately to its original morphology and physiological be- 
havior as soon as adequate aeration was again provided, so this 
sort of change was a readily reversible process. 

The study of the chicken cholera bacillus revealed another type 
of transformation, more profound because more lasting, which 
was so definitely in conflict with the dogma of the fixity of mi- 
crobial species that it must have been at first very disconcerting 
and the source of great worry. Pasteur found that cultures of 
chicken cholera could lose their ability to produce disease and 
that, moreover, they retained this modified or "attenuated" char- 
acter through subsequent generations. Thus, the chicken cholera 
bacillus could be virulent, or not, while the other characteristics 
by which it was ordinarily identified remained unchanged. Shortly 
thereafter, Pasteur also observed a similar transformation (loss 
of virulence) in the causative agents of anthrax, swine erysipe- 
las, lobar pneumonia, and rabies. Since then, this phenomenon 
has been observed with practically all microbial agents of disease. 
Virulence is not a constant and permanent attribute of certain 
microbial species, but a variable property which can be lost, and 
then again recovered, sometimes at the will of the experimenter. 

As soon as he became convinced of the validity of his observa- 
tions, Pasteur dismissed from his mind the rigid views he had 
held concerning the fixity of biological behavior of microorgan- 
isms, and immediately turned his attention to the consequences 
that this change of virulence might imply for the problem of in- 
fection. We shall describe in a following chapter the use which 


he made of attenuated cultures to vaccinate against infectious 
diseases. Let us consider at the present time the significance of 
the alterations in virulence in the study of epidemiological prob- 

The loss of virulence of the chicken cholera bacillus had been 
discovered by a chance observation. With great skill Pasteur 
worked out empirical techniques for deriving from several viru- 
lent microorganisms, modified forms which had more or less com- 
pletely lost the ability to cause disease. Of equal interest was the 
discovery that attenuated cultures could be restored to maximum 
virulence by "passing" them through certain animals. For exam- 
ple, a culture of chicken cholera which had lost its virulence for 
chickens was found to be still capable of killing sparrows and 
other small birds and, when passed repeatedly from sparrow to 
sparrow, finally regained its virulence for adult chickens. He 
obtained fully attenuated anthrax bacilli innocuous for adult 
guinea pigs but still capable of killing the newly born. When 
these bacilli were passed from the newly bom to two-day-old 
animals, then from those to three-day-old, and so on, the culture 
progressively regained its full virulence and soon became capable 
of killing adult guinea pigs and sheep. Strange as these results ap- 
pear, they serve to illustrate how much effort and ingenuity Pas- 
teur was willing to expend in establishing experimentally the phe- 
nomenon of the instability of virulence. 

Even more remarkable was the discovery that, in certain cases, 
the virulence could be changed not only quantitatively, but also 
qualitatively. Thus the pneumococcus first isolated from human 
saliva was very virulent for the rabbit, and only slightly so for the 
adult guinea pig; and yet it could be rendered less virulent for 
the former animal and much more so for the latter, merely by 
passing it through newly born guinea pigs. The results obtained 
with the microorganism of swine erysipelas were also very strik- 
ing. When the bacillus recovered from a hog was inoculated into 
the breast of a pigeon, the bird died in six to eight days; by 
inoculating the blood of this first pigeon into a second, then from 
the second to a third, and so on, the virulence increased progres- 


sively for the pigeon and at the same time for the hog. If, how- 
ever, the bacillus was inoculated into a rabbit and then passed 
from rabbit to rabbit, its virulence increased for the rabbit but 
at the same time decreased for the hog, to such an extent that ulti- 
mately the microorganism became unable to cause disease in 
the very animal host from which it had been isolated originally. 

Pasteur believed that these phenomena of variation were of 
great importance in the epidemiology of various infectious dis- 
eases. He suggested that epidemics might arise from the increase 
in virulence of a given microorganism, and also in certain cases 
from its ability to acquire virulence for a new animal species: 

Thus, virulence appears in a new light which may be disturb- 
ing for the future of humanity, unless nature, in its long evolu- 
tion, has already experienced the occasions to produce all pos- 
sible contagious diseases a very unlikely assumption. 

* e What is a microorganism that is innocuous for man, or for this 
or that animal species? It is a living being which does not pos- 
sess the capacity to multiply in our body or in the body of that 
animal. But nothing proves that if the same microorganism should 
chance to come into contact with some other of the thousands of 
animal species in the Creation it might not invade it, and render 
it sick. Its virulence might increase by repeated passages through 
that species, and might eventually adapt it to man or domesti- 
cated animals. Thus might be brought about a new virulence and 
new contagions. I am much inclined to believe that such mecha- 
nisms explain how smallpox, syphilis, plague, yellow fever, # 
cetera have come about in the course of the ages, and how cer- 
tain great epidemics appear from time to time." 

Symbiosis and parasitism are two apparently opposing mani- 
festations of interrelationships between living beings. In sym- 
biosis, two organisms establish a partnership which is of mutual 
benefit; in lichens, for example, two microscopic organisms an 
alga and a fungus live in association, the former synthesizing 
the chlorophyll, which absorbs from the sun the energy required 
for the assimilation of carbon dioxide in the air, the latter micro- 


organism extracting water, minerals, and perhaps certain essen- 
tial organic substances from the soil or from the plant which it 
uses for support. There are also many examples of symbiosis be- 
tween microorganisms and higher plants or animals. Orchids re- 
quire the presence of a fungus for the germination of their seeds; 
in legume plants, the nodules which occur on the roots are 
growths of bacteria which borrow water, minerals and carbon 
compounds from the plant and supply the latter in return with 
nitrogen derived from the air. In parasitism, by contrast with 
symbiosis, one of the members of the association exploits the 
other without contributing anything useful to its welfare. 

The distinction between symbiosis and parasitism is not always 
well defined, nor perhaps constant It appears possible that, in 
the general order of natural events, symbiotic relationships are 
now and then upset, with the result that one of the partners takes 
exclusive advantage of the association and becomes a true para- 
site; on the other hand, parasitism may be the first step of nat- 
ural relationships, and may slowly evolve into that co-operative 
association which we call symbiosis or partnership. If the evo- 
lution from parasitism to symbiosis is the general trend in nature, 
optimism is then justified, and only patience is required to see 
man become man's helpful partner. If, on the contrary, parasites 
have evolved from once helpful partnerships, it demands much 
faith to believe that man will reverse the order of nature or that 
the ancient saying Homo homini lupus * will ever become obso- 

Whatever its origin, parasitism implies that the parasite must 
find in its "host** conditions favorable for growth: adequate food, 
proper temperature and other essential living requirements. On 
the whole, bacteriologists have paid little heed to these physio- 
logical aspects of the problem of infection, despite the fact that 
infectious disease is clearly an example of parasitism. It is of 
special interest, therefore, to find that Pasteur attempted to 
analyze in biochemical terms the mechanistic basis of the para- 
sitic behavior of microbial agents. 

1 "Man is man's worst enemy." 


As will be remembered, he had grown yeast and certain bac- 
teria in nutrient fluids of known chemical composition; under his 
inspiration Raulin had defined, with great detail, the nutritional 
requirements of the fungus Aspergillus niger, thus providing the 
pattern according to which the nutrition of other microorganisms 
could be studied. Somewhat later, Pasteur had recognized that 
many of the microbial agents of disease had more complex re- 
quirements and grew well only when supplied with certain types 
of organic substances. However useful, this information was not 
sufficient to throw light on the nutritional conditions required by 
pathogenic agents for multiplication in the animal body; and, 
in fact, this problem is still unsolved today despite much increased 
knowledge. Pasteur, nevertheless, bravely attempted to apply nu- 
tritional concepts to the phenomena of parasitism, and he con- 
sidered the possibility that immunity might result from the ex- 
haustion in the host of some component essential to the growth 
of the pathogen. He even imagined that cancers might consist of 
altered tissue cells competing successfully with normal cells for 
the nutritive elements brought by the blood, and suggested means 
of treatment based on this theory. Naive as these views were, they 
deserve respect as the first statement of the problem of the nu- 
tritional relationship between parasite and invaded host. 

Pasteur's preoccupation with the influence of body temperature 
on microbial multiplication came to light in his famous contro- 
versy with Colin concerning the susceptibility of chickens to 
anthrax. Colin, a professor at the Veterinary School of Alfort, had 
acquired a certain notoriety by constantly opposing Pasteur's 
views before the Academy of Medicine. In a slow, monotonous 
and sour voice, he would endlessly reiterate his doubts concern- 
ing the validity of the evidence against spontaneous generation, 
for the role of microorganisms in putrefaction, on the etiology of 
anthrax. Pasteur having stated that birds, and notably hens, could 
not contract anthrax, Colin had hastened to say that nothing was 
easier than to give this disease to hens. This was in July 1877. 
Pasteur, who had just sent Colin a culture of the anthrax bacillus, 


begged that he would bring Mm in exchange a hen suffering from 
that disease, very likely with the malicious hope of exposing some 
technical error on the part of his opponent. The story of this epi- 
sode was told to the Academy of Medicine in March 1878. 

u At the end of the week, I saw M. Colin coming to my labora- 
tory, and even before I snook hands with him, I said, "Why, you 
have not brought me that diseased hen!*. . . 'Trust me/ an- 
swered M. Colin, "you shall have it next week.'. . . I left for 
vacation; on my return, and at the first meeting of the Academy 
which I attended, I went to M. Colin and said, 'Well, where is 
my dying hen?' T. have only just begun experimenting again,* 
said M. Colin; *in a few days I shall bring you a hen suffering 
from anthrax.* . . . Days and weeks went by, with fresh insistence 
on my part and new promises from M. Colin. One day, about two 
months ago, M. Colin acknowledged that he had been mistaken, 
and that it was impossible to give anthrax to a hen. 'Well, my dear 
colleague/ I told him, *I will show you that it is possible to give 
anthrax to hens; I shall myself, one day, bring to you at Alfort a 
hen which shall die of the disease/ 

"I have told the Academy this story of the hen which M. Colin 
had promised in order to show that our colleague's contradiction 
of our findings on anthrax had never been very serious.'* 

In reply, Colin stated before the Academy: "I regret that I 
have not been able as yet to hand to M. Pasteur a hen dying 
or dead of anthrax. The two that I had bought for that purpose 
were inoculated several times with very active blood, but neither 
of them fell ill. Perhaps the experiment might have succeeded 
later, but, one fine day, a greedy dog prevented that by eating up 
the two birds, whose cage had probably been badly closed." 

On the Tuesday following this incident, Pasteur emerged from 
the Ecole Normale, carrying a cage containing three hens, one 
of which was dead, and drove to the Academy of Medicine. After 
having deposited his unexpected load on the desk, he announced 
that the dead hen had been inoculated with anthrax two days 
before at twelve o'clock on Sunday, with five drops of culture 
of the anthrax bacillus and had died on Monday at five o'clock, 


twenty-nine hours after the inoculation. This result was the out- 
come of an original experiment. Puzzled by the fact that the 
hens were refractory to anthrax, he had wondered whether this 
resistance might not be due to the body temperature of the birds, 
known to be higher than that of animals susceptible to the disease. 
To test this idea, hens were inoculated with anthrax and then 
placed in a cold bath in order to lower their temperature. Ani- 
mals so treated died tie next day with their blood, spleen, lungs, 
and liver filled with bacilli The white hen which lay dead on the 
floor of the cage was evidence to the success of the experiment 
To show that it was not the prolonged bath which had killed it, 
a speckled hen had been placed in the same bath, at the same 
temperature and for the same time, but without infection; this 
bird was in the cage on the desk, extremely lively. The third hen, 
a black one, had been inoculated at the same time as the white 
hen, with the same culture, using ten drops of culture instead of 
five, to make the experiment more convincing; but it had not been 
subjected to the bath treatment and had remained in perfect 

A fourth experiment was carried out later to establish whether 
a hen, infected with anthrax and allowed to contract the disease 
by being placed in a cold bath, would recover if allowed to re- 
establish its ordinary body temperature by being removed from 
the bath early enough. A hen was taken, inoculated and cooled 
in a bath, until it was obvious that the disease was in full progress. 
It was then taken out of the water, dried, wrapped in cotton 
wool and placed at a temperature sufficient to allow rapid restora- 
tion of normal body temperature. To Pasteur's great satisfaction, 
the hen made a complete recovery. Thus, the mere fall of tem- 
perature from 42 C. (the normal temperature of hens) to 38 C. 
was sufficient to render birds almost as receptive to infection as 
rabbits or guinea pigs. 

Unconvinced by this experiment, or moved by his antagonism 
to Pasteur, Colin suggested on July 9, 1878, that the dead hen 
which had been laid on the desk of the Academy in the pre- 
ceding March meeting might not, after all, have died of anthrax. 


As had Liebig and Pouchet in earlier years, CoHn thus opened 
himself to the riposte. Pasteur immediately extended to trim the 
challenge of submitting their differences to a commission of the 
Academy, with the understanding that Colin himself would per- 
form the post-mortem and microscopic examination of the dead 
bird. Pasteur's experiments were repeated on July 20, and nat- 
urally yielded the results that he had forecast. CoMn ungraciously 
signed the commissioner's statement that hens inoculated with 
a culture of anthrax, then cooled in a water bath, died with a 
large number of anthrax bacilli in their blood and tissues. 

Despite the apparent simplicity of the experiment, the effect 
of temperature on the susceptibility of chickens to anthrax is cer- 
tainly a more complex phenomenon than Pasteur assumed it to be. 
True enough, the cooling of chickens by immersion in cold water 
brought their body temperature down to a level compatible with 
the growth of the anthrax bacillus, but at the same time it prob- 
ably interfered with the performance of normal physiological 
mechanisms, thus increasing the susceptibility of the animals to 
infection. The results, nevertheless, were of interest as being the 
first experimental demonstration that environmental factors in- 
fluence the course of infection, and that the presence in the body 
of a pathogenic agent is not necessarily synonymous with disease. 

A few months later, Pasteur discussed before the Academy of 
Medicine another example of the influence of physiological fac- 
tors on the behavior of microbial parasites. This new example, 
even more convincing to his audience because it had a more 
direct bearing on human infections, concerned the relation of 
oxygen to the role of the vibrion septique as an agent of disease. 
In contrast with anthrax bacilli, the vegetative cells of the vibrion 
septique cannot live in the presence of oxygen and are actually 
killed by it; only the spores survive aeration. The vibrion septique 
is widely distributed in nature, normally present in the intestinal 
tract of some animals, often present also in soil. In the intestinal 
canal it is protected from the toxic effect of air by the presence 
of immense numbers of other bacteria which are capable of utiliz- 
ing the last trace of oxygen, but it has no chance to multiply 


in normal tissues, or on a clean wound open to air. How, then, 
can it become established in tissues and cause disease? According 
to Pasteur, this happens when the conditions in the wound or 
in the tissues are such that they limit the access of air, or when 
large numbers of other bacteria exhaust the oxygen from it. Then, 
the mbfion septique finds a favorable environment and produces 
its deadly toxin in contact with tibe susceptible tissues. 

^Let a single clot of blood, or a single fragment of dead flesh, 
lodge in a comer of the wound sheltered from the oxygen of the 
air, where it remains surrounded by carbon dioxide . . . and im- 
mediately the septic germs will give rise, in less than twenty-four 
hours, to an infinite number of vibrios multiplying by fission 
and capable of causing, in a very short time, a mortal septi- 

It is common experience that insects or worms can attach them- 
selves to man, animals or plants, deriving thereby food and 
maintenance and causing at the same time annoyance and irri- 
tation, often injury and sometimes death. The first contagious 
disease shown to be caused by a minute parasite was probably 
itch (scabies), in which a barely visible anthropod insect (Sar- 
coptes scabiei) burrows a microscopic tunnel into the human epi- 
dermis. In this case, the meaning of the term "parasite" appears 
obvious and its application to disease justified. Physicians and 
experimenters found little difficulty in extending the concept of 
parasitism from the attack by insects to infections caused by 
fungi. In the ergot disease of rye, the mal del segno of silkworms, 
the f avus and herpes tonsumns of man, one could imagine that the 
disease was due to some direct injury inflicted by the fungus 
parasite on the superficial tissues of the victim. In the case of 
bacterial diseases, however, it became much harder to form a 
concrete picture of the parasitic relationship. How could such 
microscopic beings, detectable in the body fluids and tissues only 
by the most exacting microscopic study, do damage to the power- 
ful and well-organized body structures of man and animal? What 
weapons could they use to inflict injury profound enough to ex- 


press itself in disease and death? Pasteur offered some tentative 
and preliminary answers to these questions in Ms early papers on 
contagion, but unfortunately he was prevented from developing 
them further by the pressure of his subsequent studies on vac- 

He regarded disease as a physiological conflict between the 
microorganism and the invaded tissue. According to him, for 
example, the anthrax bacilli compete for oxygen with the red 
blood corpuscles and cause them to suffer a partial asphyxia; the 
dark color of the blood and of the tissues, which is one of the most 
characteristic signs of anthrax at the time of death, would thus be 
an expression of oxygen deficiency. In the case of chicken cholera, 
he assumed that "the microbe causes the severity of the disease 
and brings about death through its own nutritional require- 
ments. . . . The animal dies as a result of the deep physiological 
disorders caused by the multiplication of the parasite in its 

Pasteur established that disease-producing microorganisms can 
also cause symptoms and death by secreting soluble poisons. He 
passed the blood of an animal infected with anthrax through a 
plaster filter in order to remove the anthrax bacilli from it. When 
added to fresh normal blood this filtrate brought about an imme- 
diate agglutination of the red cells similar to that which occurs in 
the animal body during the course of the natural infection. This 
was the first indication that physiological disturbances can be 
caused by the products of bacterial growth, even in the absence 
of the living microorganisms themselves. 

Even more convincing was the demonstration that the causa- 
tive agent of chicken cholera produces a soluble toxin. One of 
the most striking symptoms of this disease is the appearance of 
somnolence in the birds before death. 

'The diseased animal is strengthless, tottering, with drooping 
wings. The feathers of the body are raised and give it the form of 
a ball. An invincible somnolence overcomes the animal. If one 
compels it to open its eyes, it behaves as if coming out of a deep 
slumber and soon closes its eyelids again; usually death comes 


after a silent agony without the animal having moved at all. At 
most, it will beat its wings for a few seconds." 

A culture grown in chicken broth, filtered so as to free it of 
living germs, is unable to cause true chicken cholera. However, 
injection under the skin of large amounts of this filtrate repro- 
duces in the bird many of the symptoms of the natural disease. 
The chicken . . . takes the shape of a ball, becomes motionless, 
refuses to eat and exhibits a profound tendency to sleep similar 
to what is observed in the disease produced by the injection of 
the living microbe itself. The only difference consists in the fact 
that sleep is lighter than in the real disease; the chicken wakes 
up at the slightest noise. This somnolence lasts approximately four 
hours; then the chicken again becomes alert, raises its head, and 
clucks as if nothing had happened. . . . Thus, I have acquired the 
conviction that during the life of the parasite there is produced a 
narcotic which is responsible for the symptom of sleepiness char- 
acteristic of chicken cholera." 

Although Pasteur was inclined to believe that death was caused 
by the multiplication of the microorganisms in the body of the 
fowl, and not by the effect of the soluble toxin, he concluded his 
remarkable observation by the following words: TE shall attempt 
to isolate the narcotic, to determine whether it can produce death 
when injected in sufficient dose, and to see whether, in this 
eventuality, death would be accompanied by the pathological 
lesions characteristic of the natural disease. 9 * 

This sentence could have heralded a new phase in Pasteur's 
scientific life. He had struggled hard to prove that contagious 
diseases were caused by living microorganisms. As soon as this 
fact had been established, he had asked himself the next question. 
Through what mechanism do these living agents cause disease? 
This query had brought him back to the analysis of disease in 
terms of chemical reactions. He had postulated that the life of 
the infectious agent interfered with the biochemical processes 
of the infected animal; he had demonstrated the production of 
soluble toxins, and had planned to "isolate" them as chemical 
substances. Prosecution of these two aspects of the problem 


would have led him Into the most profound questions pertain- 
ing to the pathogenesis of infectious disease, questions which to 
a large extent remain unanswered today. 

Unfortunately, time was running out and there were other 
pressing problems to be solved. The memoir in which Pasteur 
had described the soluble toxin of chicken cholera was devoted 
chiefly to a discussion of immunity against the disease, and to 
the possibility of vaccinating against it. This problem monopo- 
lized the energy of his remaining years, and he never came back 
to those visionary concepts which had thrown the first light on 
the mechanism of the physiological interrelationships between 
living things. 


Medicine, Public Health and the 
Germ Theory 

False facts are highly injurious to the progress of 
science, for tibey often endure long; but false views, if 
supported by some evidence, do little harm, for every- 
one takes a salutary pleasure in proving their false- 


THE germ theory of disease constitutes one of the most impor- 
tant milestones In the evolution of medicine. It dispelled some of 
the mystery and much of the terror of contagion; it facilitated and 
rendered more precise the diagnosis of disease; it provided a ra- 
tional basis for the development of prophylactic and therapeutic 
procedures. These great achievements should not lead one to 
assume that progress in the control of infectious disease dates 
from the bacteriological era. In reality, many of the most devastat- 
ing scourges have been conquered without the benefit of labora- 
tory research, and some have even disappeared without any con- 
scious effort on the part of man. 

In the course of recorded history, overwhelming epidemics have 
arrested invading armies on the march, decimated populations, 
disorganized the social fabric, changed the pattern of civiliza- 
tions but mankind has survived. Life has proved flexible enough 
to triumph over yellow fever, influenza, typhus, plague, cholera, 
syphilis, malaria, even when there were available no effective 
measures to combat disease. Less dramatic, but fully as astonish- 
ing as the spontaneous and often sudden termination of the great 


epidemics, is the continuous downward trend of certain diseases 
in the course of centuries. 

Leprosy was once universally prevalent and remains today a 
widespread and destructive disease in many parts of the world* 
Witness to Its importance in Biblical times are the precise laws 
in Leviticus regulating the behavior of the lepers, and of society 
toward them. The Hebrew belief in the contagiousness of leprosy 
survived in medieval times and led the Church to pronounce the 
leper dead to the world, leaving iim only the consolation of im- 
mortality. By a symbolic ritual, the "unclean" was ordered to 
keep away from his fellow men, a measure which probably con- 
tributed to minimizing the spread of contagion. Homes of mercy 
were established all over Christendom to care for the lepers as 
well as to isolate them, these "lazarettos'* having been precursors 
of our hospitals. Perhaps as a result of this segregation, probably 
also because of a general improvement in the standards of living, 
leprosy has been on the decline throughout Europe since the 
Renaissance, and is now practically nonexistent in our commu- 
nities. There are still many "uncleans" among us, but it might be 
toward the control of syphilis and gonorrhea that the teaching 
of Leviticus would be directed today. 

Not so long ago, tuberculosis was the Great White Plague, the 
"captain of all men of death" for the white race. In Boston, New 
York, Philadelphia and Charleston in London, Paris and Berlin 
all available statistics reveal tuberculosis mortality rates of 500 
or higher per 100,000 inhabitants in the year 1850. Some time 
around 1860, the number of deaths from the disease began to de- 
crease in Europe and North America, and it has continued to 
decrease ever since except for brief interruptions in the downward 
trend, interruptions associated with two world wars. In 1947, 
tuberculosis mortality rates were below 40 per 100,000 population 
in several countries and were still decreasing. Thus, in many 
places, the toll of deaths due to tuberculosis had decreased more 
than tenfold in less than a century, a spectacular event that has 
excited endless discussions among students of public health. The 
decrease began before the discovery of the tubercle bacillus, long 


before there were available any specific methods of prevention or 
cure. Western civilization is slowly, but perhaps not surely, gain- 
ing in its fight over tuberculosis, without being too certain of the 
circumstances to which it owes its success. For equally mysterious 
reasons scarlet fever is on the wane; fifty years ago a frequent 
cause of death, it is today a relatively mild disease. Syphilis spread 
through Europe like a prairie fire during the fifteenth and six- 
teenth centuries. Its course was then rapid, and often fatal 
unlike that of the frequently mild and slowly progressive disease 
of our days. In this case, again. Western civilization took the dis- 
ease in stride and learned to live with it. Indeed, the contagion 
may have made European culture burn with a brighter light, if it 
be true, as claimed by certain medical writers, that a correlation 
exists between syphilis and genius. 

Only feeble hypotheses have been offered to account for the 
fact that society has gained the upper hand over certain diseases 
without knowing anything as to their cause or mode of transfer. 
It is usually assumed that better nutrition, housing and sanitation, 
as well as other improvements in the general standard of living, 
have played a large part in the conquest of leprosy and tubercu- 
losis. This view certainly contains much truth, but there is also an 
element of human conceit in attributing the disappearance of 
certain diseases only to technological improvements. Many factors 
affect the course of epidemic cycles and some of them are beyond 
human control for the time being. As a population, the rats of 
Bombay have become resistant to the plague bacillus which has 
been present among them for many centuries, whereas the rats 
of New York, Paris and London are still susceptible to it; perhaps, 
like twentieth-century man, the Bombay rat prides himself on the 
achievements of his civilization in having overcome rat plague. 

The conquest of malaria provides the most convincing evidence 
that material civilization can wipe out certain infectious diseases 
unaided by microbiological or other medical sciences. The Cam- 
pagna Eomana was free of malaria as long as Roman hearts and 
muscles were robust enough to drain its marshes. Two centuries 
ago, malaria was rampant in the Ohio valley, and pioneers suf- 


fered or died of it wMe clearing the green forests. It has virtually 
disappeared today, because malaria always recedes before a vig- 
orous agrarian society. Its disappearance from our Middle West 
is only an accidental by-product of the clearing of the land, and 
not the result of a planned campaign. Extensive fanning rendered 
the country unsuitable for the mosquitoes that transmit malaria, 
and the disease became extinct, just as did many of the forms of 
wild life native to the primitive forests. 

All leaders of wandering men, of roaming tribes or conquering 
armies, have had to become sanitarians to prevent the spread of 
the diseases of filth. Moses enacted strict sanitary regulations for 
camp life before he could lead his people across the desert; the 
wandering Jew codified in the Old Testament many of the pre- 
cepts which are still essential to the control of crowd diseases. 
As stated by the historian Garrison: "The ancient Hebrews were, 
in fact, the founders of prophylaxis, and the high priests were 
true medical police." 

Although plague long constituted the major menace to Euro- 
pean life, it had almost disappeared from Western Europe by the 
nineteenth century. Cholera and typhoid fever became the out- 
standing diseases associated with filth, while typhus also remained 
prevalent, especially in jails* Through the efforts of public- 
minded citizens, most of them not physicians, around 1850 so- 
ciety slowly began to take an active interest in a more salubrious 
life clearing slums, eliminating filth, providing fresh air and 
abundant, clean water. Edwin Chadwick first sold to England 
the "sanitary idea," the concept that it is possible by controlling 
the social environment to suppress the forces of disease instead 
of accepting them as an inevitable fate. The extreme degree of 
filth with which the reformers had to cope can be imagined from 
the following account left by an observer who visited the tene- 
ments of Glasgow in 1855. "We entered a dirty low passage like 
a house door, which led from the street through the first house 
to a square court immediately behind, which court, with the ex- 
ception of a narrow path around it leading to another long pas- 
sage through a second house, was used entirely as a dung recep- 


tacle of the most disgusting kind. Beyond this court, the second 
passage led to a second square court, occupied in the same way 
by its dunghill; and from this court there was yet a third passage 
leading to a third court and third dung heap. There were no 
privies or drains there, and the dung heaps received all filth which 
the swarm of wretched inhabitants could give; and we learned 
that a considerable part of the rent of the houses was paid by the 
produce of the dung heaps." A similar situation was found at 
Inverness. TThere are very few houses in town which can boast 
of either water closet or privy, and only two or three public 
privies in the better part of the place exist for the bulk of the 
inhabitants." At Gateshead, "The want of convenient offices in 
the neighborhood is attended with many very unpleasant circum- 
stances, as it induces the lazy inmates to make use of chamber 
utensils, which are suffered to remain in the most offensive state 
for several days, and are then emptied out of the windows." 
These conditions had their counterpart in every country and were 
described for New York City in the survey prepared by Stephen 
Smith in 1865. It told of streets littered with garbage and paper. 
Youngsters armed with brooms made a small income by sweep- 
ing a path through the muck for those who wanted to cross 
Broadway near City Hall. 

Even in the midst of prevailing filth, the individual can to some 
extent protect himself against cholera, typhoid and dysentery by 
a never-ending attention to the water that he drinks, the food 
that he eats, and the objects that he touches. It is told for exam- 
ple that in the Philippines the orthodox Chinese who had re- 
tained the ancestral habit of drinking nothing but tea made from 
boiled water remained free of cholera during the epidemics 
which killed the Filipinos surrounding them. But this eternal 
vigilance is hardly compatible with a normal life, and the con- 
trol of filth diseases obviously had to come from a general im- 
provement of hygiene. This was the point of view emphasized 
by Chadwick in a celebrated report on the Sanitary Condition 
of the Labouring Population of Great Britain, published in 1842. 
He concluded: 


"That the various forms of epidemic, endemic, and other dis- 
ease caused, or aggravated, or propagated chiely amongst the 
labouring classes by atmospheric impurities, produced by decom- 
posing animal and vegetable substances, by damp and filth and 
close overcrowded dwellings, prevail amongst the population in 
every part of the kingdom, whether dwelling in separate houses, 
in rural villages, in small towns, in the larger towns as they have 
been found to prevail in the lowest districts of the metropolis. 

"That such disease, wherever its attacks are frequent, is always 
found in connexion with the physical circumstances above speci- 
fied, and that where those circumstances are removed by drain- 
age, proper cleansing, better ventilation and other means of 
diminishing atmospheric impurity; the frequency and intensity 
of such disease is abated; and where the removal of the noxious 
agencies appears to be complete, such disease almost entirely 

"The primary and most important measures, and at the same 
time the most practicable, and within the recognized province 
of administration, are drainage, the removal of all refuse of habi- 
tations, streets, and roads, and the improvement of the supplies 
of water." 

Although unaware of the role of microorganisms as agents of 
disease, the men who brought about the "great sanitary awaken- 
ing" often succeeded in introducing practices of community life 
which greatly limited the spread of contagion. Suffice it to mention 
again the German hygienist Max von Pettenkofer, who did so 
much to rid Munich of typhoid fever without the benefit of 
chlorine or of vaccination, simply by cleaning up the city and 
providing pure water. It was at that time, also, that Florence 
Nightingale effected her reforms of hospital sanitation during the 
Crimean War, and laid the foundation for her campaign against 
unhygienic conditions in the British Army in India. Unbeliever in 
disease germs that she was, she nevertheless knew how to control 
most of them. 

Eradication of certain diseases has been achieved by a con- 


scions attack not on the causative microbial agent; but on its insect 
vector. It is well known that tie opening of the Panama Canal 
became a possible enterprise only after General Gorgas had rid 
the surrounding tropical country of every breeding place for the 
mosquitoes which transmit yellow fever and malaria. Similarly, 
typhus, one of the most devastating infections of all previous 
armed conflicts, was rendered insignificant during the last World 
War by the systematic debusing of exposed individuals and by 
the widespread use of the insecticide DDT. In these cases, the 
control techniques did not directly affect the mierobial agent of 
the disease but only the insect that transfers it to man. 

Societies have attempted to protect themselves against the 
spread of infection by the enactment of quarantine policies. In 
the time of great epidemics, men were forbidden to move from 
the stricken areas into unaffected districts; ships were not allowed 
to unload their passengers until the threat of contagion had dis- 
appeared. Today the protection of ropes, to prevent the passage 
of rats ship-to-shore, and the treatment of airplanes with in- 
secticides after landing, in an attempt to destroy mosquitoes, are 
examples of quarantine measures based on factual knowledge of 
the modes of spread of infections. 

It is questionable, however, whether quarantine as formerly 
practiced ever played a significant part in minimizing the spread 
of great epidemics of plague and cholera. Convinced as he was 
that microorganisms by themselves could not cause the disease 
unless many other environmental factors were also present, Pet- 
tenkofer naturally minimized the value of these measures and 
cited numerous examples of their failure. There are today many 
students of public health who share his skepticism. The existence 
of reservoirs of contagion, of the apparently healthy "carriers" 
mentioned in the preceding chapter, imposes severe technical 
limitations to any attempt at preventing the entrance of the in- 
fective microorganisms in a community. Rabies constitutes per- 
haps the only case for which there is convincing evidence that 
certain countries have been successful in protecting themselves 
against the introduction of a human disease. Except in Central 


America, where the vampire bat can transfer the virus of rabies 
to man and animals, the disease is contracted cMely through the 
bite of rabid dogs and wolves. By practicing a severe control over 
the introduction of dogs from the outside, as well as over the 
stray animals within their borders, England, Australia and Ger- 
many have managed to protect themselves more or less com- 
pletely against the disease. Here again, this achievement was in- 
dependent of the rise of the microbiological sciences. 

Thus, many techniques for the partial control of infectious 
disease had been developed before the bacteriological era. The 
possibility of approaching the problem of control from several 
different angles stems from the fact that the establishment of dis- 
ease is dependent upon many unrelated factors, involving the 
infective microorganism, its physical and biological carriers and 
vectors, the physiological and psychological conditions of the 
individuals exposed to it, as well as the physical and social char- 
acteristics of the environment. This very multiplicity of factors 
often makes it possible to attack infectious disease at several in- 
dependent levels. The germ theory led to a more accurate under- 
standing of the circumstances under which host and parasite 
come into contact, and thus permitted the formulation of rational 
control policies of greater effectiveness than those devised em- 
pirically in the past Knowledge of the properties and behavior of 
the infective microorganism often suggested means to attack it, 
either before or after it had reached the human body. Such is 
the practice of immunization which consists in establishing a 
specific resistance against a given contagious disease by exposing 
the body, under very special conditions, to the infective agent, 
to an attenuated form of it, or to one of its products. The science 
of immunity is one of the most direct outcomes of the germ 
theory; and it is the more surprising, therefore, to realize that 
immunization had been practiced during antiquity, long before 
anything was known of the role of microorganisms as agents of 
disease; vaccination against "Oriental sore" and against smallpox 
are among the most successful and ancient achievements of pre- 
ventive medicine. 


There exists, in many Eastern countries, an infection of the skin 
known under the name of "Oriental sore" or "Aleppo boil/' caused 
by the protozoan Leishmania tropica. It develops following the 
bite of insects, often leaving unsightly sores. As an attack of the 
disease confers lasting immunity, it became the practice in en- 
demic areas to infect young children on concealed parts of the 
body, in order to prevent disfiguring lesions of the face. In a 
similar manner, inoculation with smallpox was widely practiced 
in ancient Oriental civilizations. Jenner introduced vaccination 
with cowpox in 1796, and this procedure is, even today, one of the 
most effective examples of preventive immunization. So impor- 
tant was Jenner's achievement in stimulating Pasteur's work that 
it is best to reserve the detailed discussion of it for a separate 

For the reasons outlined in the preceding pages, it is far less 
simple than commonly believed to assess the effect of the germ 
theory on the control of infectious diseases. The number of deaths 
due to typhus, cholera, typhoid, tuberculosis, had begun to de- 
crease at a very appreciable and, in certain cases, at a startling 
rate before the causative agents of these diseases had been dis- 
covered. This statement is not intended to minimize the impor- 
tance of the revolution which microbiological sciences brought 
about in medical thinking, but rather to provide a historical basis 
on which to describe the nature of this revolution, and to evaluate 
its consequences for human health. 

The problems of surgical infections, childbirth fever and in- 
testinal diseases offer striking illustrations of the influence of the 
germ theory on the growth of medicine and hygiene. 

In the past, infections had always been the chief cause of the 
mortality following operations of any sort. Of the 13,000 amputa- 
tions performed in the French Army during the Franco-Prussian 
War in 1870-1871, no less than 10,000 proved fatal. Here and 
there, individual surgeons attempted to lessen mortality by clean- 
liness and by the employment of special washes for wounds, but 
all these attempts were empirical and in general did not avail. It 


was Pasteur's demonstration that bacteria were responsible for 
fermentations and putrefactions which gave the clue that Lister 
followed to reform surgical practice. 

Lister's attention was called to Pasteur's work on the role of 
microorganisms in putrefaction sometime around 1864, by the 
chemist Anderson. He was well prepared to understand the sig- 
nificance of Pasteur's observations because, as mentioned earlier, 
his father had early made him familiar with the microbial world. 
If, as Lister postulated, microorganisms cause wound suppuration, 
just as they cause fermentation and putrefaction., they must be 
excluded at all costs from the hands of the surgeon, from his in- 
struments, and from the very air surrounding the operating field. 
To achieve this Lister used a spray of phenol throughout the 
operations, taking his lead from the fact that this substance was 
then employed for the disinfection of sewage and excreta. Within 
a short time, he acquired the conviction that his antiseptic tech- 
nique prevented suppuration and permitted healing **by first in- 
tention* in the majority of cases. 

This antiseptic method was based on the hypothesis, derived 
from Pasteur's writings in the 1860's, that wound contamination 
originated chiefly from microorganisms present in the air. As he 
began to frequent hospital wards, however, Pasteur became 
more and more convinced that the importance of the air-borne 
microorganisms had been exaggerated and that the most impor- 
tant conveyors of infection were the persons who took care of the 
sick. He emphasized this point of view in a famous lecture de- 
livered before the Academy of Medicine. 

"This water, this sponge, this lint with which you wash or cover 
a wound, deposit germs which have the power of multiplying 
rapidly within the tissues and which would invariably cause the 
death of the patient in a very short time, if the vital processes of 
the body did not counteract them. But alas, the vital resistance is 
too often impotent; too often the constitution of the wounded, his 
weakness, his morale, and the inadequate dressing of the wound, 
oppose an insufficient barrier to the invasion of these infinitely 
small organisms that, unwittingly, you have introduced into the 


injured part. If I had the honor of being a surgeon, impressed as 
I am with the dangers to which the patient is exposed by the 
microbes present over the surface of all objects, particularly in 
hospitals, not only would I use none but perfectly clean instru- 
ments, but after having cleansed my hands with the greatest care, 
and subjected them to a rapid flaming, which would expose them 
to no more inconvenience than that felt by a smoker who passes 
a glowing coal from one hand to the other, I would use only lint, 
bandages and sponges previously exposed to a temperature of 
130 to 150 Cr 

This memorable statement has become the basis of aseptic sur- 
gery, which aims at preventing access of pathogenic agents to the 
operative field rather than trying to Mil them with antiseptics 
applied to the tissues. 

One might think that, by 1878, the germ theory would be suffi- 
ciently well-established to make Pasteur's warnings needless. In 
reality, the sense of aseptic technique was still at that time com- 
pletely foreign to many enlightened physicians, as is revealed by 
the following account by Loir: "One day, at the Hdtel Dieu, Pro- 
fessor Richet was asked by Pasteur to collect pus from one of the 
surgical cases. He was doing his ward rounds with a soiled white 
apron over his black dress suit. Interrupting himself, he said, *We 
are going to open this abscess; bring me the small alcohol lamp 
which M. Pasteur used yesterday to flame the tube in which he 
collected some pus for his experiment We shall now sacrifice to 
the new fashion and flame the scalpel/ and with a wide gesture, 
which was characteristic of him, he wiped the scalpel on the 
soiled apron twice, and then attacked the abscess." 

In contrast to the carelessness of his medical colleagues, Pas- 
teur carried his concern for aseptic precautions to the most ex- 
treme degree. The odd advice to the surgeons that they flame 
their hands before operating on their patients reflected a proce- 
dure which was part of routine technique in his laboratory until 
1886. Pasteur's habit of cleaning glasses, plates and silverware 
with his napkin before every meal is easier to understand when 
placed in the atmosphere created by the recent discovery of dis- 


ease germs. He had shown that the vibrion septique, commonly 
present in the intestinal content of animals and in soil, could also 
be the cause of violent death if It reached susceptible tissues. He 
had seen in the blood and organs of women dying of childbirth 
fever a streptococcus which was similar in appearance to that 
found in many fermenting fluids. In this bewildering new world 
which unfolded before him, there were at first no criteria to judge 
where danger might be lurking. True enough, he was aware of 
the fact that in addition to the dangerous microorganisms, there 
are many which are completely innocuous, but as no techniques 
were then available to differentiate the black sheep from the 
white, he deemed it advisable to exert the utmost caution in 
everyday life. 

Before the advent of the germ theory, the problem presented 
by childbirth fever was in many respects similar to that of wound 
infections. Out of 9886 pregnant women who came for confine- 
ment at the Maternite Hospital in Paris between 1861 and 1864, 
1226 died of the disease, and the situation was as tragic in all 
lying-in hospitals of Europe. In Boston, Oliver Wendell Holmes 
had taught in 1843 that childbirth fever was an infectious disease, 
and that the infection was carried by the hands of the physician 
or midwife from one patient to another. There was much opposi- 
tion to his theory from Meigs of Philadelphia, who resented 
what he considered Holmes's imputation that the physician's 
hands were not clean, and who quoted a number of cases of in- 
fection that had occurred in the practice of the great Dr. Simpson 
of Edinburgh, an "eminent gentleman." To this, Holmes replied: 
**Dr. Simpson attended the dissection of two of Dr. Sidney's cases 
(puerperal fever), and freely handled the diseased parts. His 
next four childbed patients were affected with puerperal fever, 
and it was the first time he had seen it in his practice. As Dr. 
Simpson is a gentleman, and as a gentleman's hands are clean, 
it follows that a gentleman with clean hands may carry the 

Holmes's warnings were unheeded, as were those of his con- 


temporary, Semmelwels, who preached the same gospel in Buda- 
pest. Semmelweis had become convinced that childbirth fever 
was a wound infection caused by the contamination of the raw 
surface left in the uterus after the birth of the child, and that the 
infection was transmitted by the unclean hands of the physicians 
and students who examined the women during labor. Merely by 
requiring students to wash their hands in a solution of chloride 
of lime before making an examination, Semmeiweis succeeded in 
decreasing the death rate in his service by 90 per cent. Neverthe- 
less he also was opposed by his colleagues; tormented by hostility 
and injustice everywhere, he lost his mind and died without hav- 
ing convinced the medical world of his discovery, 

It appears incredible, today, that physicians should have re- 
mained blind for so long to the contagiousness of childbirth fever, 
and that one of the authoritative speakers in the Paris Academy 
of Medicine could speak with scorn of contagion as late as 1879. 
It was in the course of this discussion that Pasteur dared to inter- 
rupt the speaker and sketched on the blackboard the germs 
streptococci which are the most common cause of the disease. 
Acceptance of the germ theory made of childbirth fever a pre- 
ventable disease. Cleanliness became the supreme virtue of the 
lying-in hospital when finally physicians recognized that the in- 
fection could be carried to the patient by her attendants. 

The public-minded citizens who had championed the great 
sanitary awakening of the nineteenth century had attributed to 
filth the crowd diseases particularly the intestinal disorders. 
Pure water, pure food, pure air and pure soil appeared to them 
as an adequate formula to prevent disease and promote health. 
It was obvious to many physicians, however, that the problem 
was not so simple. All had observed that many rural areas re- 
mained free of infectious fevers such as tuberculosis, typhoid or 
cholera despite the overwhelming prevalence of filth. It was also 
familiar knowledge that disease often reigned in places where the 
advocates of "pure" and salubrious living conditions had appar- 
ently every reason to be satisfied. The view that filth is not syn- 


onymous with disease was defended in England by William Budd, 
the greatest epidemiologist of the nineteenth century, who had 
been the first to establish beyond doubt that intestinal fever was 
caused by a "virulent poison cast off by the diseased intestine" 
and capable of propagating itself. Budd took the opportunity of 
"the Great Stench" of London which occurred during the hot 
summer months of 1858 - to illustrate in a forceful manner the 
fact that organic putrefaction, alone, cannot cause disease. 

"The Occasion was no common one. An extreme case, a gigantic 
scale in the phenomena, and perfect accuracy in the registration 
of the results three of the best of all the guarantees against 
fallacy were all combined to make the induction sure. For the 
first time in the history of man, the sewage of nearly three million 
people had been brought to seethe and ferment under a burning 
sun, in one vast open cloaca lying in their midst The result we all 
know: Stench so foul, we may well believe, had never before as- 
cended to pollute this lower air. Never before, at least, had a 
stink risen to the height of an historic event. Even ancient fable 
failed to furnish figures adequate to convey a conception of its 
thrice Augean foulness. For many weeks, the atmosphere of Par- 
liamentary Committee rooms was only rendered barely tolerable 
by the suspension before every window, of blinds saturated with 
chloride of lime, and by the lavish use of this and other disin- 
fectants. More than once, in spite of similar precautions, the law 
courts were suddenly broken up by an insupportable invasion of 
the noxious vapour. The river steamers lost their accustomed 
traffic, and travellers, pressed for time, often made a circuit of 
many miles rather than cross one of the city bridges. 

"For months together, the topic almost monopolized the public 
prints. Day after day, week after week, The Times teemed with 
letters, filled with complaint, prophetic of calamity, or suggesting 
remedies. Here and there, a more than commonly passionate ap- 
peal showed how intensely the evil was felt by those who were 
condemned to dwell on the Stygian banks. At home and abroad, 
the state of the chief river was felt to be a national reproach. India 
is in revolt, and the Thames stinks/ were the two great facts 


coupled together by a distinguished foreign writer, to mark the 

climax of a national humiliation. 

"Members of Parliament and noble lords, dabblers in sanitary 
science, vied with professional sanitarians in predicting pesti- 
lence. But, alas for the pythogenic theory, when the returns were 
made up, the result showed not only a death rate below the aver- 
age, but, as the leading peculiarity of the season, a remark- 
able diminution in the prevalence of fever, diarrhoea and the 
other forms of disease commonly attributed to putrid emana- 

After Koch had discovered the cholera vibrio in 1883 and 
Gaffky identified the typhoid bacillus in 1884, it became obvious 
that even the dirtiest water or most polluted atmosphere would 
not cause cholera or typhoid if it did not contain the specific 
causative microorganism, and obvious also that the worst agents 
of disease could lurk in the "cleanest" and most transparent water. 
This knowledge made it possible to plan for the supply of safe 
water on a more rational basis, the criterion of safety being no 
longer the absence of foul smells, but the freedom from living 
agents of disease. To achieve this end, sources of uncontaminated 
water were secured wherever possible, arrangements were made 
for adequate filtration, and chlorine was added to water in con- 
centrations sufficient to kill the vegetative forms of bacteria. The 
understanding of the nature of contamination also permitted the 
method of water purification to be adapted to changing circum- 
stances. Thus, because the cysts of the amoeba which causes 
dysentery are more resistant to chlorine than are bacteria, the 
sterilization of water in certain tropical regions demands steps 
more drastic than those which suffice where these cysts are un- 
likely to occur. Microbiological sciences also provided convenient 
techniques for the control of the safety of water. Even where the 
amount of organic matter is too small to permit ready detection 
by chemical means, bacteriological analysis is often capable of 
revealing the presence of living organisms and thus provides a 
guide in tracing sources of contamination. 

The causative microorganisms of typhoid and cholera have not 


changed, and men are still susceptible to them, yet the great epi- 
demics of the past are not likely to occur again under normal con- 
ditions in our cities. The sanitarians of the mid-nineteenth century 
had made typhoid and cholera less frequent in the Western world; 
armed with bacteriological knowledge, the modem public health 
officer is now in a position to complete the victory and to gain 
absolute control over these diseases if the community is willing to 
support him. Thanks to the germ theory, the blind campaign 
against filth has been replaced by an attack on the sources of in- 
fection, based on knowledge of the nature and modes of trans- 
mission of the agents of disease. In the words of Charles V. 
Chapin, who was head of the Department of Public Health in 
Providence, Rhode Island, at the beginning of the present cen- 

"It will make no demonstrable difference in a city's mortality 
whether its streets are clean or not, whether the garbage is re- 
moved promptly or allowed to accumulate, or whether it has a 
plumbing law. . . . We can rest assured that however spick and 
span may be the streets, and however the policeman's badge may 
be polished, as long as there is found the boor careless with his 
expectoration, and the doctor who cannot tell a case of polio 
from one of diphtheria, the latter disease, and tuberculosis as 
well, will continue to claim their victims. , . . Instead of an in- 
discriminate attack on dirt, we must learn the nature and mode of 
transmission of each infection, and must discover its most vul- 
nerable point of attack." 

Pasteur never took an active part in the formulation of public 
health regulations; he left to others the duty to administer the 
land which he had conquered. Chemotherapy - that is, the treat- 
ment of established disease by the use of drugs is another field 
of medical microbiology which he did not till. He had not ignored 
it, but he did not believe that it was the most useful approach to 
the control of infection. "When meditating over a disease, I never 
think of finding a remedy for it, but, instead, a means of prevent- 
ing it." This is a policy which enlightened societies are slowly 


learning to adopt, one which the wise men of China have under- 
stood if it be true that they advise paying doctors to prevent 
sickness, rather than to treat it. It is also possible that Pasteur was 
kept from working on chemotherapy by another reason that ap- 
pears as a casual sentence in one of his reports on the silkworm 

"My experiments (on silkworms) have brought the knowledge 
of the prevailing diseases to a point where one could approach 
scientifically the search for a remedy. . . . However, discoveries 
of this nature are more the result of chance than of reasoned 
orderly studies. 

Tlie discovery of the use of sulfur for treating the oidium of 
the grapevine was so little scientific that the very name of its 
author has remained unknown." 

Pasteur was right in his opinion that useful drugs are usually 
discovered by accident, or at least by purely empirical methods, 
but he was wrong in believing that the discovery of the use of 
sulfur had remained unknown for this reason. If the names of 
those who first worked out methods for the treatment of plant 
diseases are so rarely mentioned, it is not because their work was 
unscientific, but because men consider of great importance only 
that which directly affects their own persons. Historians work 
hard to identify the individuals who introduced quinine in human 
medicine, but pay little attention to those who developed tech- 
niques to save our crops. 

One could quote many examples to illustrate Pasteur's state- 
ment that the discovery of drugs has often been the result of 
chance. The beneficial effects of salicylic acid in rheumatic fever, 
and of digitalis in dropsy, were first recognized and utilized on 
the basis of empirical observations. The uses of quinine and of 
ipecacuanha (emetine) were discovered by American Indians 
long before anything was known of the cause of malaria and 
amoebic dysentery, diseases for which these drugs are so effec- 
tive. The discovery of the usefulness of sulfonamides came out of 
the empirical testing of countless dyes in countless experimental 
animals infected with a variety of infectious agents; today, after 


fifteen years of intensive research, there is still doubt as to the 
mechanism by which these drugs control infection. 

It is one of Pasteur's own accidental observations which ushered 
in the most spectacular phase of discoveries in the field of therapy 
of infectious disease. He had observed that cultures of anthrax 
bacilli contaminated with common bacteria often lose their ability 
to establish disease in experimental animals, and he rightly con- 
cluded that these common bacteria produced some substance 
inimical to the disease agent. Was it sheer luck, or the desire to 
comment on this interesting phenomenon, or real vision, that in- 
spired him to predict a great future for his chance observation? 
"Neutral or slightly alkaline urine is an excellent medium for the 
bacilli [of anthrax]. . . . But if ... one of the common aerobic 
microorganisms is sown at the same time, the anthrax bacilli grow 
only poorly and die out sooner or later. It is a remarkable thing 
that the same phenomenon is seen in the body even of those ani- 
mals most susceptible to anthrax, leading to the astonishing result 
that anthrax bacilli can be introduced in profusion into an animal, 
which yet does not develop the disease. . . . These facts perhaps 
justify the highest hopes for therapeutics." 

The hint was not lost. Immediately after him, and ever since, 
many bacteriologists have attempted to find in nature micro- 
organisms capable of producing substances effective in the treat- 
ment of infectious disease. The story of this search does not be- 
long here. The title of its most important chapter, ^Penicillin," is 
sufficient to call to mind the accidental detection of a mold which 
inhibited the growth of staphylococcus, and then the organized 
effort of pathologists, bacteriologists, chemists and technologists 
to make the miraculous drug available to the world. Initially, it 
was a chance observation which revealed the existence of peni- 
cillin; but again it was true that "chance favors only the prepared 
mind.'* In this case, the mind favored by chance had been pre- 
pared by years of familiarity with bacteriological lore. Not only 
did the germ theory permit the discovery of penicillin; it also 
guided at every step those who worked to define the immense 
possibilities of the drug in the treatment of disease. Today, it still 


guides the search for other substances capable of interfering with 
the pathogenic behavior of the microbial agents of infection. 

In addition to suggesting that certain common microorganisms 
might be used in the therapy of infection, Pasteur had also the 
extraordinary idea of advocating the utilization of microbial life 
for the control of animal and plant parasites. The first suggestion 
of this nature concerns phylloxera, a plant louse that was then 
infesting and ruining the vineyards of France and of the rest of 
Europe. It appears as a casual laboratory note dictated to Loir 
by Pasteur in 1882: 

To find a substance which could destroy phylloxera either at 
the egg, worm, or insect stage appears to me extremely difficult 
if not impossible to achieve. One should look in the following 

The insect which causes phylloxera must have some contagious 
disease of its own and it should not be impossible to isolate the 
causative microorganism of this disease. One should next study 
the techniques of cultivation of this microorganism, to produce 
artificial foci of infection in countries affected by phylloxera." 

Pasteur never tried to establish the practical usefulness of this 
suggestion in the case of phylloxera, but he came back to the idea 
five years later under the following circumstances. During the 
latter part of the nineteenth century, the settlers in Australia and 
New Zealand introduced rabbits and Bares from Europe into 
their countries. The land and climate proved so favorable to the 
rabbits that these animals multiplied at an extraordinary rate, 
reaching immense numbers and destroying crops and pastures. 
Hunting, trapping and poisoning proved without avail against 
the new plague. So great was the destruction of crops that the 
Government of New South Wales offered in August 1887 a prize 
of 25,000 to anyone demonstrating an effective method for the 
extermination of rabbits. 

In November, Pasteur wrote a long letter to the editor of the 
Paris newspaper Le Temps, where he had read the announcement 
of the prize, and outlined his views on the subject: 


"So far, one has employed mineral poisons to control this 
plague. ... Is not this the wrong approach? How could mineral 
poisons deal with animals that multiply at such an appalling rate? 
The poisons kill only at the place where one deposits them. Is it 
not preferable to use, in order to destroy living beings, a poison 
also endowed with life, and also capable of multiplying at a great 

"I should like to see the agent of death carried into the burrows 
of New South Wales and of New Zeaknd by attempting to com- 
municate to rabbits a disease that might become epidemic." 

He pointed out that chicken cholera is extremely fatal to rabbits 
and could be given to the animals by feeding infected foodstuffs, 
and he suggested practical techniques by which the method could 
be applied on a large scale in the field. 

In January 1888 he reported in the AnndLes de Tlnstitut Pasteur 
several laboratory experiments proving the susceptibility of rab- 
bits to infection by feeding and by contact, and he suggested the 
following procedure: "Cut the grass around the rabbit burrows 
and gather it with rakes in a place readily accessible to the rab- 
bits, before they come out in the evening. This grass, properly 
contaminated with culture of the chicken cholera bacillus, would 
be eaten by the animals as soon as they came across it." 

He received at that time from Madame Pommery, owner of 
the champagne firm, a letter advising him that rabbits had be- 
come a great nuisance in the wine cellars, and that none of the 
means used against them had succeeded in checking their multi- 
plication. Pasteur immediately sent Loir to the Pommery estate 
to carry out the antirabbit campaign that he had outlined. On 
Friday December 23, Loir spread the culture of chicken cholera 
on alfalfa around the burrows, Madame Pommery wrote on De- 
cember 26: "Saturday morning (the day following the contami- 
nated meal), nineteen dead rabbits were found outside the bur- 
rows. . . . On Monday morning sixteen more cadavers were 
found, and no living rabbit could be seen. Some snow had fallen 
during the night and yet no rabbit tracks were to be found near 
the cellars." 


Further correspondence from Madame Pominery, on January 5, 
revealed that the cadavers of many rabbits could be found wher- 
ever one looked in the burrows, and confirmed the full success of 
the test 

On the strength of these results, Pasteur sent Loir to Australia 
to organize a campaign of destruction of rabbits by creating an 
epidemic of chicken cholera among them, but the test was never 
carried out, as the Department of Agriculture of Australia refused 
to give the necessary authorization. Loir nevertheless stayed in 
Sydney for several years, organizing a microbiological institute 
for the Australian government and conducting a program of vac- 
cination of farm animals against anthrax. 

A few attempts, patterned after Pasteur's experiments on the 
effect of chicken cholera on rabbits, have since been made to 
control animal and plant plagues by the use of other microbial 
parasites. Best known are those utilizing bacteria pathogenic for 
rats and mice, and also for certain plant pests. Although encourag- 
ing results have been obtained, they have not lived up to the early 
expectations. It is relatively easy to cause the death of animals 
with infected food, but it is extremely difficult to establish an 
epidemic with a progressive course. A few years ago, an attempt 
was made in Australia to introduce the virus of infectious myxo- 
matosis on an island infested with rabbits. In this case again, the 
disease did not become established in the rabbit population al- 
though myxomatosis is known to be a highly fatal disease for these 
animals. As pointed out repeatedly in preceding pages, the spread 
of any infection is conditioned by a multitude of factors, many 
of them unknown; epidemics often break out in a mysterious 
manner, but they also subside spontaneously for equally obscure 
reasons. If this were not the case, leprosy, tuberculosis, plague, 
cholera, typhus, influenza, poliomyelitis and countless other 
scourges would have long ago annihilated the human race. The 
factors which limit the spread of epidemics have been responsible 
so far for the failure of the microbiological warfare devised by 
Pasteur to control animal plagues. Fortunately they limit also the 


destructive potentialities of microbiological warfare between 
men, at least until more knowledge is available. 

There is a tragic irony in tibe fact that one of the last of Pas- 
teur's experimental studies should have been devoted to the utili- 
zation of a technique by which contagious disease can be used to 
destroy life. Today, further progress in the control of infection 
depends to a large extent upon a more thorough understanding 
of the factors which govern the spread of epidemics and it is 
this very knowledge which is also needed to make of biological 
warfare the self-reproducing weapon of future wars. This pros- 
pect, however, should not be held as an argument to minimize 
the beneficial results of microbiological sciences. For, as Francis 
Bacon said, < I the debasement of arts and sciences to purposes 
of wickedness, luxury, and the like, be made a ground of objec- 
tion, let no one be moved thereby. For the same may be said of 
all earthly goods; of wit, courage, strength, beauty, wealth, light 
itself, and the rest/* 

The centers of medical enlightenment in classical Greece were 
the rival schools located on the islands of Cos and Cnidus. Cnidian 
medicine was based on the diagnosis of the different diseases, 
which it attempted to describe and classify as if they constituted 
well-defined entities. In some respects, the bacteriological era is 
the fruition of this ancient biology: the different fevers, by them- 
selves, may not appear to be absolutely independent and separate 
entities, but the specific microorganisms which cause them cer- 
tainly are. 

Medicine in Cos was concerned with the patient rather than 
with the disease, and considered the environment as of decisive 
importance in conditioning the behavior and performance of the 
body. This doctrine is symbolized in the person, legendary or 
historical, of Hippocrates, and was codified in his treatise on "Air, 
Water and Places," where there occurs no clear reference to con- 
tagion. Medicine remained Hippocratic in inspiration until late 
in the nineteenth century, and its progress has long been hindered 


by the lack of awareness that microbial parasites can become 
established in the fluids and tissues of the body, and cause pro- 
found alterations of structure and functions. Hippocratic medicine 
had failed to take into account the fact that microorganisms con- 
stitute one of the most important factors of man's environment. 

After 1877, the pendulum swung widely in the opposite direc- 
tion, and physicians, as well as the lay public, became obsessed 
with the thought of disease germs. Today, many medical scholars 
lament the fact that, under the influence of the germ theory, too 
much emphasis has been placed on the microorganisms which 
cause disease, and too little on the effects exerted by hereditary 
constitution, climate, season and nutritional state on susceptibility 
to infection. In this justified criticism there is often implied the 
belief that Pasteur, who was not a physician, was responsible for 
a distortion of medical thinking. In reality, the complete sacrifice 
of the physiological to the bacteriological point of view is not 
Pasteur's guilt but that of the medical bacteriologists who fol- 
lowed him during the so-called "Golden era of bacteriology." True 
enough, Pasteur had to limit his own experimental work to the 
study of microorganisms and of their activities, but this limita- 
tion was the consequence of the shortness of days and of life, and 
not of the narrowness of his concepts. On many occasions, he 
referred to the importance of constitution and environment for the 
occurrence of disease, and to his desire to investigate them. Un- 
fortunately, he was prevented from doing it by the fierceness of 
the controversies concerning the participation of microorganisms 
in disease, and by the enormous amount of experimental work 
required to bring unassailable proof of his views. This effort 
monopolized all his energies, even though it did not satisfy his 

For the sake of effective experimentation, Pasteur designed his 
studies on infection and vaccination in such a way that the viru- 
lence of the microorganism or the state of acquired immunity was 
the dominant factor in his tests. But many a time although this 
was seldom recalled by later workers he referred in passing to 
the effect of environmental factors, and to the significance of con- 


stitutional susceptibility and resistance, on the course and out- 
come of contagious disease. He had shown that the susceptibility 
of chickens and of rabbits to anthrax could be respectively in- 
creased or decreased by lowering or raising the body tempera- 
tures of these animals. He had postulated that resistance to infec- 
tion could depend on the absence of certain chemical elements in 
the tissues. He had repeatedly emphasized that different races, or 
even different individuals within one given species, exhibit vary- 
ing degrees of "vital resistance," and that this resistance can be 
still further modified by changing the conditions of life. 

"If you place this child [born of tuberculous parents] under 
good conditions of nutrition and of climate, you have a good 
chance to save him from tuberculosis. . . . There exists, I repeat 
it, a fundamental difference between the disease in itself and its 
predisposing causes, the occasions which can bring it about . . . 

"How often the constitution of the wounded, his weakened con- 
dition, his mental state . . . are such that his vital resistance is 
not sufficient to oppose an adequate barrier to invasion by the 
infinitely small." 

All through his studies on silkworms, as we have pointed out, 
he devoted much attention to the influence of general hygienic 
conditions in the nurseries, and lie came to believe that this was 
the most important approach to the control of pebrine and 

"If I were ... to undertake new studies on silkworms, I 
should like to concern myself with the conditions which increase 
their general vigor. ... I am convinced that it would be possible 
to discover means to give the worms a higher level of physiologi- 
cal robustness and increase thereby their resistance to accidental 
maladies. . . . 

To increase the vigor of the silkworms by exposing the eggs 
to the cold of winter or to an artificial cold would be an achieve- 
ment of very great importance." 

Rudimentary as these thoughts are, they reveal clearly how 
much importance he attributed to the physiological state of well- 
being as a factor in resistance. 


His concern for this problem led him to devote his first lecture 
on physics and chemistry at the Ecole des Beaux Arts in Paris "to 
the important question of the sanitation and ventilation ... of 
hospitals, theaters, schools, private dwellings and meeting rooms/' 
Far from being hypnotized with the idea that microorganisms are 
the only factors of importance in medicine, Pasteur knew that 
men as well as animals, in health or in disease, must always be 
considered as a whole and in relation to their environment. Medi- 
cine can best help the patient by co-operating with the vis medica- 
trix naturae. 

Many needful discoveries remain to be made before the role of 
microorganisms in disease is completely known and controlled; 
the Pasteurian chapter is not closed, and will never be forgotten. 
But acceptance of the germ theory of disease was only one step 
in the evolution of medicine. Knowledge of the existence and 
properties of the microbial parasites is making it easier to study 
the fundamental processes of the living body, its intrinsic strength 
and weaknesses, its reaction to the environment. Medicine can 
again become Hippocratic now that contagion is no longer a 
mysterious and unpredictable threat to the life of man. Thanks 
to the germ theory, it has become possible to analyze with greater 
profit the part played by nature and nurture in health and in dis- 
ease, as well as the pervasive influence of "Air, Water and Places.** 


Immunity and Vaccination 

Arts and sciences are not cast in a mold, but are 
formed and perfected by degrees, by often handling 
and polishing, as bears leisurely lick their cubs into 


SMAJLLPOX was probably introduced into Europe from the Orient 
by the Crusaders and by the Saracens when they invaded Spain. 
It increased in prevalence from the sixteenth century onward and 
became the most important infectious disease of that time. 
According to reports* only five out of every thousand persons 
escaped infection, and one out of four died of it in seventeenth- 
century England. More than half the population had obvious 
pockmarks, and blindness due to smallpox was of common 
occurrence; Macaulay has depicted in graphic terms the atmos- 
phere of terror engendered by "the Scourge" in those days. 
"The smallpox was always present, filling the churchyards with 
corpses, tormenting with constant fears all whom it had not yet 
stricken, leaving on those whose lives it spared the hideous traces 
of its power, turning the babe into a changeling at which the 
mother shuddered, and making the eyes and cheeks of a betrothed 
maiden objects of horror to the lover." 

Although the frequency of pocking and blindness during the 
seventeenth and eighteenth centuries may have been exaggerated, 
there is no doubt that smallpox was then a deadly and loathsome 
disease all over Europe. The enthusiasm displayed by Thomas 
Jefferson in a letter that he wrote to Jenner congratulating him 


on the discovery of vaccination gives a measure of the importance 
of smallpox in the society of Ms time: 

Medicine has never before produced any single improve- 
ment of such utility. . . . You have erased from the cal- 
endar of human afflictions one of its greatest. Yours is the 
comfortable reflection that Mankind can never forget that 
you have lived; future generations will know by history only 
that the loathsome smallpox has existed, and by you had 
been extirpated. 

Smallpox had invaded the American continent with the Con- 
quistadores early in the sixteenth century, a Negro slave in 
Hemando Cortex's army being credited with transmitting the in- 
fection to the Inca populations in Mexico. The disease spread 
among them without restraint and was perhaps more effective 
than Spanish arms and valor as an instrument of conquest; 

For sixty days it raged with such death-bringing virulence 
that the period of the raging of hueyzahuatl, or Great Pest, 
fixed itself as a central point in the chronology of the natives. 
In most districts half the population died, towns became 
deserted, and those who recovered presented an appearance 
which horrified their neighbors. . . . x 

The story repeated itself when the North American Indians in 
their turn came into contact with the European invaders. Like 
tuberculosis and alcoholism half a century later, smallpox played 
havoc with the red man and contributed to his defeat by the 
whites, who were more resistant to the forces of destruction they 
had brought with them. The Europeans soon realized that they 
had an unsuspected ally in smallpox and did not hesitate to use 
it willfully to further their aims. Seeing Indian villages and tribes 
decimated by the new scourge, the invaders tried to accelerate 
the spread of the infection by introducing contaminated objects 
into the settlements of their enemies. The following quotations 
from official colonial documents leave no doubt that the European 

1 Quoted in Steam, W. E. and Steam, A. E., The Effect of Smallpox on the 
Destiny of the Amerindian (Boston: Bruce Humphries, Inc., 1945.) 


soldiers and the colonists were aware of the contagiousness of 
smallpox and of the susceptibility of the Indians to the disease. 

You will do well to try to inoculate the Indians by means 
of blankets as well as to try every other method that can 
serve to extirpate this exorable race. 

Out of our regard for them [le., two Indian chiefs] we 
gave them two blankets and a handkerchief out of the small- 
pox hospital. I hope it will have the desired effect. 

I will try to inoculate . . . with some blankets that may 
fall into their hands, and take care not to get the disease 
myself. 2 

Moralists consider it a sign of the degeneracy of our times that 
scientists dare discuss the possibility of biological warfare for the 
next armed conflict. They lack historical memory, for conquerors 
have never concerned themselves with moralists, nor waited for 
scientists to use the forces of nature for the prosecution of their 
plans. So it was that long before the atomic bomb and the spread- 
ing of bacteria through the air were ever thought of, the soldiers 
of the European kings and the New England Puritans used small- 
pox to destroy the Indians; and before them the medicine men 
and soldiers of early civilizations had learned to poison or con- 
taminate wells and food supplies. There is nothing new under 
the sun. 

It has been known from all antiquity that second attacks of 
smallpox are rare and that persons who have once had the disease 
can nurse patients with safety. This knowledge led to the idea 
that, since it was almost impossible to avoid the infection, it might 
be desirable to have it at one's own convenience. Thus grew the 
practice of "inoculation" or "validation," which consisted in inoc- 
ulating individuals in a good state of health with pustule material 
from mild cases of smallpox and in placing them under condi- 
tions believed to allow the disease to run its course with a mini- 
mum of risk. Inoculation against smallpox is said to have been 
practiced in China, India and Persia since remotest times but it 
was not until 1717 that Lady Montagu, wife of the British am- 

2 Steam, W. E., and Steam, A. E., op. cit. 


bassador to Turkey, introduced it from Constantinople into Eu- 
rope. Variolation was first practiced in America by a Dr. Boylston 
of Boston in 1721. He had been encouraged by Ms friend Cotton 
Mather, who had learned from slaves that the practice was com- 
mon in Africa. The disease induced by inoculating smallpox virus 
under the skin of a well person was usually mild and had a low 
mortality; it was as contagious as normally contracted smallpox, 
however, and required the isolation of the patient for a number 
of weeks. For this reason, friends arranged to be inoculated at the 
same time and to spend the period of seclusion in each other's 
company. Despite all care, the practice of variolation remained 
dangerous and never gained wide acceptance. 

It is claimed that Sanskrit texts mention that an attack of cow- 
pox exerts a protective effect against subsequent exposure to 
smallpox, but this fact was lost sight of until the observation made 
by Jenner at the end of the eighteenth century. Edward Jenner 
was a country practitioner of lively and inquiring mind, as wit- 
nessed by his notebooks in which records of weather, facetious 
epigrammatic verses, and entertaining drawings compete for 
space with accounts of the habits of birds and of the doings of 
his patients. His observations on natural history had given him 
scientific distinction and he had been elected a Fellow of the 
Royal Society. In particular, he was known for having seen a 
young cuckoo bird pitch a newly hatched sparrow out of the 
nest, and for having recognized on the back of the young cuckoo 
a peculiar depression "formed by nature for the design of giving 
a more secure lodgment to the egg of the hedge sparrow or its 
young one when the young cuckoo is employed in removing 
either of them from its nest" 

In eighteenth-century England there was some belief that per- 
sons having cowpox, an infection which presented some similarity 
to smallpox, were thereby rendered incapable of contracting the 
latter disease. It is reported that Jenner was led to study the 
matter by the statement of a Gloucestershire dairymaid who had 
come to him as a patient. When he suggested that she was suffer- 
ing from smallpox, she immediately replied: "I cannot take the 


smallpox because I have had the cowpox." Jenner attempted to 
give scientific foundation to the popular belief by observing the 
reaction of cowpoxed persons to inoculation with smallpox. There 
were many chances to make such observations, for cowpox was 
then a fairly common disease and it was an accepted medical 
practice to infect smallpox into human beings for prophylactic 
purposes. Jenner reported that the local reaction was transitory, 
that no fluid-containing vesicle was produced on the skin, and 
that there was no constitutional disturbance. He thus satisfied 
himself, if not all others, "that the cowpox protects the human 
constitution from the infection of the smallpox." 

In May 1796, he gave cowpox to James Phipps, a boy eight 
years old, and later inoculated him with virulent smallpox virus. 
The boy failed to contract smallpox and Jenner hastened to report 
this epoch-making observation: 

"The first experiment was made upon a lad of the name of 
Phipps in whose arm a little vaccine virus was inserted, taken 
from the hand of a young woman who had been accidentally 
infected by a cow. Notwithstanding the resemblance which the 
pustule, thus excited on the boy's arm, bore to variolous inocula- 
tion yet as the indisposition attending it was barely perceptible, 
I could scarcely persuade myself the patient was secure from the 
Small Pox. However, on his being inoculated some months after- 
wards, it proved that he was secure/' 

Thus was introduced into the Western world the practice of 
immunization against smallpox by the injection of virus material 
originating in the cow; the word "vaccination," under which the 
method came to be known, is derived through "vaccine" from 
vacca, a cow. 

After having shown that inoculation with cowpox could "vac- 
cinate" against smallpox, Jenner had experienced anxiety for 
fear it might always remain necessary to return to the cow to 
obtain the vaccine. He believed that cowpox originated in the 
cow from the hands of a milker infected with smallpox, and that 
the human disease became transformed into cowpox by passage 
through the animal. So confident was he of having discovered a 


technique for eliminating smallpox that he wondered whether 
cowpox material might not become unavailable for human vac- 
cination. He therefore attempted to vaccinate from arm to arm, 
in the hope that cowpox virus would not lose its vaccinating po- 
tency, nor acquire excessive virulence by being passed through 
the human body. He inoculated a child with material from the 
teat of a cow; from the sore on this child's arm another child 
was inoculated and the process was repeated from one child to 
another, up to the fifth removed from the cow. Three of these 
children were later inoculated with smallpox and all three proved 
resistant to the disease, demonstrating the possibility of carrying 
the vaccination from arm to arm. 

Were Jenner's own observations really adequate to justify such 
an important conclusion? Some epidemiologists have questioned 
it and one of them, Greenwood, has referred to Jenne/s writings 
as "just the sort of rambling, discursive essay, containing acute ob- 
servations mixed up with mere conjectures, which an unsys- 
tematic field naturalist might be expected to produce/' In fact, 
Jenner's first paper on his discovery was rejected by the Royal 
Society in 1797 with a friendly admonition that such incomplete 
studies would injure his established reputation. 

Jenner extended his paper, and published it as a pamphlet in 
1798 under the tide An Inquiry into the Causes and Effects of the 
Variolae,, a Disease Discovered in Some of the Western Counties 
of England, Particularly Gloucestershire, and known by the 
Name of Cow Pox. 

It is not without interest that, like Jenner's first paper on vac- 
cination, John Snow's first report, demonstrating that cholera is 
water-borne, had to be published at the expense of its author. 
Official academies are more likely to exhibit enthusiasm over the 
improvements of the commonplace than to recognize the un- 
expected when it is first brought to them. But academic indiffer- 
ence did not keep Jenner from becoming convinced of the abso- 
lute effectiveness of vaccination and he stated his faith in no 
uncertain terms. "At present, I have not the most distant doubt 
that any person who has once felt the influence of perfect cow- 


pox matter would ever be susceptible to that of the smallpox." 
However, many accidents soon occurred that could have shaken 
his faith. As the method began to be widely used, many patients 
developed bad ulcers at the site of vaccination, and some con- 
tracted smallpox despite the treatment In May 1811 the Hon- 
orable Robert Grosvenor, whom Jenner himself had vaccinated 
ten years before, fell ill with an extremely severe case of small- 
pox. The young man recovered but his case created an enormous 
sensation in medical and lay circles and led to bitter controver- 
sies. Nevertheless, the efficacy of vaccination soon became widely 
accepted and rewards in addition to fame came to Jenner for his 
discovery. In 1802, Parliament voted him 10,000 and again in 
1806, 20,000 for his achievement, while learned societies joined 
with sovereigns in paying him honor. 

Jenner soon had many followers in England but it was perhaps 
in America that the method received the most vigorous support. 
Benjamin Waterhouse in Boston took up the cudgels for vac- 
cination, as Cotton Mather had done for inoculation almost a 
century earlier. Having received vaccine virus from England, he 
vaccinated his own family in July 1800 and dared expose his 
children to infection in the smallpox hospital in order to dem- 
onstrate that they were immune. In 1801, he sent some of Jen- 
ner*s vaccine to President Thomas Jefferson, who had his own 
family vaccinated, as well as some of their neighbors and a few 

Opposition to Jenner continued in some medical circles even 
after cowpox vaccination had become established throughout the 
world as a standard practice. As late as 1889, Creighton, eminent 
English historian of infectious diseases, dismissed Jenner as a 
*Vain, imaginative, loose-thinking person" and his claims as mere 
roguery. In his book The Wonderful Century, Wallace described 
vaccination as one of the dark spots of the age, not only denying 
its efficacy, but also expressing great doubts as to its innocuous- 
ness. Although no trained epidemiologist would take this view 
today, all recognize that it is not a simple matter to evaluate 
statistically the effectiveness of vaccination. Like other infec- 


tious diseases, smallpox probably undergoes fluctuation unpre- 
dictable both in prevalence and in severity. As vaccination is 
now widely practiced throughout the civilized world, it is diffi- 
cult L-O determine how the disease would behave in an unvac- 
clnated population; hence it is impossible to determine exactly 
what role vaccination plays in the control of the disease. 

For a balanced judgment of the case, we may turn to the con- 
clusions reached by Greenwood in his study of vaccination. 

"I have, indeed, as an individual, almost as strong a conviction 
that recent vaccination is a thoroughly adequate defence against 
the risk of taking smallpox as anti-vaccinists have that it is worth- 
less as a defence and otherwise pernicious, but I know of no data 
by means of which I could estimate the measure of such ad- 
vantage. ... I conclude by inferring from the statistical evidence 
which I have discussed that Jenner was, directly or indirectly, the 
means of saving many hundreds of thousands of lives. That is a 
less grandiose conclusion than some others have reached, yet, I 
submit, quite enough to entitle Englishmen to take pride in the 
recollection that Jenner was their countryman." 

The success of vaccination encouraged many efforts during the 
middle of the nineteenth century to use similar methods of pre- 
ventive inoculation against other diseases such as measles, plague, 
sypliilis and pleuropneumonia of cattle. Indeed, a proposal to 
inoculate all the youth of France with syphilis actually reached 
the Paris Academy of Medicine, where it gave rise to a lively 
discussion. One of the chief proponents of this measure was 
Auzias-Turenne who, as we shall presently see, played some 
indirect part in the formulation of Pasteur's views on the prob- 
lems of immunity. 

Like many others who preached the germ theory of disease 
be Tore Pasteur and Koch, Auzias-Turenne is now forgotten. And 
yet his views, which he presented indefatigably in many articles 
arid lectures, so impressed some of his contemporaries that they 
republished them after his death in the form of a large book 
entitled La Syphilfeation. 

Auzias-Turenne advocated immunization of the youth of the 


world against syphilis by inoculating material from soft chancre, 
which he regarded as an attenuated form of the disease. Ac- 
cording to him, soft chancre bore to s} r philis the same relation 
that cowpox does to smallpox. It was with this message that he 
expected to gain immortality, but he also had much to say con- 
cerning other infectious diseases such as anthrax, cholera, small- 
pox, rabies, and pleuropneumonia of cattle. His statements illus- 
trate the point of view held by some medical men before Pasteur 
and Koch had definitely established that the "viruses of disease" 
were living microorganisms. Auzias-Turenne accepted as estab- 
lished the variability in virulence of infective agents, the possi- 
bility of immunizing against certain contagious diseases, and the 
view that immunity was due to the exhaustion in the body of 
some substance required by the causative agent of the disease. All 
these concepts were to be recast in experimental terms by Pasteur 
two decades later. 

From a lecture delivered in October 1865 before the Academy 
of Medicine and reprinted in La Syphilisation, one can glean the 
following statements which summarize the philosophy of infec- 
tion reached by Auzias-Turenne: 

The virus is always identical to itself, variable in inten- 
sity, transmissible, i.e., capable of reproducing itself after 
a given time of incubation in the proper organism. . . . 

Viruses derive what they need from the infected or- 
ganism and often end by exhausting the latter . . . they 
either destroy it or abandon it for lack of food. . . . 

Viruses can undergo variations in intensity. , . . 

A virus can be regenerated in a good terrain in which it 
multiplies, whereas it can be weakened by an unfavorable 
terrain. . . . But a good terrain becomes exhausted when 
It carries the virus for too long a time. . . . 

Viruses are transmissible. They pass from one individual 
to the other like parasites. . . . 

Contagion presupposes a direct contact of the virus with 
the organism. Infection does not involve a direct contact; the 
virus may be carried through a medium which is usually 
the atmosphere. The virus survives in it without being de- 


composed and thus passes from one place or one individual 
to another. 

We have established . * . that inoculation can be used 
for the prevention of contagious pleuropneumonia of cat- 
tle. We shall now show that it can also be used as a thera- 
peutic measure. 

Let us walk into a stable where pleuropneumonia is pre- 
vailing. . . . The animals can be divided into three groups. 

1. Those in which the symptoms of the infection 
are already evident. . . . 

2. Those in which the disease exists in a state of 
latency or incubation. . . . 

8. Those which have not yet been affected by 

the virus. . . . 

Let us inoculate into these animals some virus taken from 
the lung. ... In animals of the first group . . . the inocu- 
lation will be without detectable effect. It will have a cura- 
tive effect in the animals of the second group . . . and the 
effect will be preventive in the animals of the third group. 

La Syphilisation was published in 1878 and, through family 
relationships, a copy fell into the hands of the young Adrien Loir, 
nephew of Pasteur, who immediately gave the book to his uncle. 
According to Loir, Pasteur was much interested in Auzias- 
Turenne's writings. He kept the book at home in a special drawer 
of his desk, and often read it, even copying whole sentences from 
it It is possible that Pasteur was encouraged to attempt immuni- 
zation of dogs and human beings after infection with the rabies 
virus by Auzias-Turenne's claims on therapeutic immunization in 
cattle pleuropneumonia. In 1878, however, he was well along in 
his studies on immunity and had already begun to work on rabies; 
Auzias-Turenne's book, therefore, probably served him as a con- 
crete basis on which to anchor his meditations at home rather 
than as the source of new ideas. 

Speaking of the plague that destroyed one fourth of the Greek 
population during the Peloponnesian Wars, Thucydides reported 
that "the sick and dying were tended by the pitying care of those 
who had recovered, because they knew the course of the disease 


and were themselves free from apprehensions. For no one was 
ever attacked a second time, or not with a fatal result*" 

Pasteur knew that one attack of certain diseases conferred a 
definite immunity against another attack of the same disease and 
he had been much impressed by Jenner's discovery of vaccina- 
tion. The problem of immunity was constantly in his mind and 
he continually wondered why Jennerian vaccination had re- 
mained an isolated fact in medicine. There was, at this time, 
much debate in the Paris Academy of Medicine concerning the 
relation of smallpox to cowpox. Were the two diseases completely 
independent one from the other, or was the latter, as believed by 
Jenner, a form of smallpox which had become modified by pas- 
sage through the cow? Pasteur followed the debate with intense 
interest and used to tell his collaborators: ^We must immunize 
against the infectious diseases of which we can cultivate the 
causative microorganism/* 

It was an accident which gave the clue to the solution of the 
problem. Pasteur had begun experiments on chicken cholera in 
the spring of 1879, but a trivial difficulty came to interrupt the 
work after the summer vacation; the cultures of chicken cholera 
bacillus that had been kept in the laboratory during the summer 
failed to produce disease when inoculated into chickens. A new, 
virulent culture obtained from a natural outbreak was inoculated 
into new animals, and also into the chickens which had resisted 
the old cultures. The new animals, just brought from the market, 
succumbed to the infection in the customary length of time, thus 
showing that the culture was very active. But to the surprise of 
all, and of Pasteur himself, almost all the other chickens survived 
the infection. Be it the result of his reading and incessant pon- 
dering on the facts of immunity, or a product of the creative 
imagination which so often permitted him to guess the solution 
of a problem without adequate evidence, Pasteur immediately 
recognized in this accidental occurrence an analogy with cowpox 

The simple observation that chickens inoculated with an 
avirulent culture of the chicken cholera bacillus were thereby 


rendered resistant to a fully virulent culture was made seventy 
years ago and its consequences have continued to grow in im- 
portance ever since. To make more emphatic the analogy be- 
tween his and Jenner's discoveries, Pasteur chose to describe the 
new phenomenon under the name of 'Vaccination." Thus, as is 
the wont of many words, the meaning of "vaccination" had 
evolved from the description of a concrete procedure into the 
expression of an abstract concept. By transferring to man pox 
material obtained from the cow, Jenner had so modified the 
human constitution as to render it no longer receptive to small- 
pox. Pasteur recognized that this effect was the manifestation 
of a general law, and that the old cultures of chicken cholera 
which had become "attenuated" during the summer had brought 
about a transformation of the animal economy which made it less 
receptive to the virulent form of the microorganism. Jenner's dis- 
covery was only a special case of a general immunization pro- 
cedure; vaccination was the art of specifically increasing the 
resistance of the body to an inimical agent. 

The discoveries of Jenner and Pasteur have implications which 
transcend immunological science. They reveal in what subtle 
manner and how profoundly the nature of living things can be 
affected by influences that reach them from the external world. 
Man or fowl, once having received a minute amount of material 
from cowpox or from the culture of a bacterium, are indelibly 
marked by this apparently trivial experience; they thereby 
become somewhat different living beings. There exists a bio- 
chemical memory which is no less real than the intellectual and 
emotional memory, and perhaps not essentially different. Immuno- 
logical science has provided techniques to detect, and in a cer- 
tain measure to control, a few of those permanent alterations. 
At the other end of the spectrum of human reactions, experi- 
mental psychology is beginning to investigate the permanent al- 
terations of the psyche which often result from apparently trivial 
external events, alterations which experience and literature have 
long recognized. Who can doubt that the gap which today sepa- 
rates the immunologist from Pavlov and Marcel Proust will some- 


day be breached, that a time will come when one can recapture 
and reconstruct from a distant biological Temps perdu the com- 
plex of biochemical happenings which make of each living thing 
a unique event in nature? 

"It is characteristic of experimental science," Pasteur wrote, 
"that it opens ever-widening horizons to our vision." While per- 
ceiving in the distance the promised land toward which he travels, 
the scientist must accept with humility his slow, limited and tedi- 
ous task; he may dream of the green pastures of natural philos- 
ophy, but he must till patiently the small patch in space and time 
where fate has placed him. This, Pasteur accepted, and he set 
himself with diligence to clear the new land which had just been 
revealed to him. 

Pasteur's discovery had merely suggested that one could obtain 
a vaccine capable of insuring protection against chicken cholera; 
it only extended to a bacterial disease a phenomenon already 
known in the case of the virus disease smallpox. There was at 
that time no factual information concerning the origin of cowpox; 
and the speculative view that it was a form of smallpox modified 
by passage through the cow had not led to any technique by 
which other agents of disease could be attenuated for the purpose 
of immunization. Pasteur realized immediately that his observa- 
tions on chicken cholera brought the phenomena of immunity 
within the range of study by microbiological techniques. As he 
could cultivate the causative bacillus of chicken cholera in vitro, 
and as attenuation of the bacillus had occurred spontaneously in 
some of his cultures, Pasteur became convinced that it should be 
possible to produce vaccines at will in the laboratory. Instead of 
depending upon the chance finding of naturally occurring immu- 
nizing agents, as cowpox for smallpox, vaccination could then be- 
come a general technique, applicable to all infectious diseases. 
Within die incredibly short period of four years, Pasteur suc- 
ceeded in demonstrating the practical possibilities of this vision- 
ary concept in the cases of chicken cholera, anthrax, swine ery- 
sipelas and rabies. 


He had attributed the attenuation of the chicken cholera bacil- 
lus to the deleterious effect of air and particularly of oxygen dur- 
ing aging of the culture. Indeed cultures maintained in glass tubes 
sealed off in the flame retained their virulence for several months 
whereas they lost their activity more rapidly in tubes closed only 
with cotton plugs. By taking advantage of these observations, 
Pasteur obtained a series of cultures of intermediate virulence 
that he could grow in his bouillons, maintaining unchanged their 
characteristic degree of attenuation and their vaccinating prop- 
erties. As mentioned in a preceding chapter, these findings ap- 
peared in conflict with the doctrine of the fixity of microbial 
species. Nevertheless, as soon as he became convinced of its valid- 
ity, Pasteur turned the fact of variability of virulence into one of 
the central tenets of his subsequent investigations and applied it 
systematically in order to obtain attenuated cultures for the pur- 
pose of vaccination. 

He had once made an observation which suggested that vac- 
cination against anthrax might be possible. A group of eight sheep 
had been maintained for a prolonged period of time in a pasture 
where an animal dead of anthrax had been buried. When inocu- 
lated with a virulent anthrax culture, several of these animals had 
survived, whereas normal sheep had all died of the same inocula- 
tion. As Pasteur knew that chickens fed upon food contaminated 
with the chicken cholera bacillus do not invariably die, and that 
those which survive are often found resistant to subsequent in- 
oculation with a virulent culture, he postulated that ingestion of 
the microorganism determined in certain cases a mild disease 
which induced a state of resistance against severe infection. Later 
studies suggested that cows which had survived an attack of an- 
thrax could withstand inoculation with large amounts of virulent 
anthrax material. TheSe facts incited Pasteur to attempt to pre- 
pare a vaccine capable of producing immunity against anthrax 
without inducing severe disease. Immediately, an unexpected dif- 
ficulty arose when attempts were made to attenuate the culture, 
for the anthrax bacillus produces spores which cannot readily 
undergo any modification. It was therefore necessary to pre- 


vent the formation of spores and at the same time to keep the 
bacilli alive. This was first accomplished by adding certain anti- 
septics to the culture and later by keeping it in a shallow layer at 
42-43 G. After eight days under these conditions the bacilli be- 
came harmless for guinea pigs, rabbits and sheep. Before com- 
pletely losing their virulence, however, they passed through all 
degrees of attenuation, and each of these could be preserved by 
cultivation in ordinary media as had been done in the case of the 
chicken cholera organism. 

Pasteur found it advisable to conduct anthrax vaccinations in 
two steps. First a preparatory inoculation of a culture of very low 
virulence was given, followed twelve days later by a more viru- 
lent "second vaccine" which conferred a higher level of immunity. 
This technique invariably made possible the protection of guinea 
pigs, rabbits and sheep against infection with the most virulent 
form of anthrax bacilli. Within a few months, Pasteur undertook 
to demonstrate the effectiveness of prophylactic vaccination by 
a large-scale public test on farm animals. This was the famous 
experiment of Pouilly le Fort, and the details of this dramatic epi- 
sode will be described later. A few weeks after his triumph at 
Pouilly le Fort, Pasteur was the star of the International Medical 
Congress in London, and there he propounded, in the course of 
lii$ address, the use of the words "vaccine** and "vaccination" to 
render homage to "the merit and immense services rendered by 
one of the greatest men of England, your Jenner." 

In association with Thuillier, he had also undertaken the study 
of swine erysipelas. The isolation of the bacterial organism was 
easy, but its attenuation to a level adequate for practical vaccina- 
tion presented new problems owing to the different susceptibili- 
ties of the various races of pigs. The remarkable fact was estab- 
lished, however, that the bacterium became attenuated for the 
pig by passage from rabbit to rabbit and it was the culture 
adapted to this animal species that became the source of the vac- 
cine used for immunization of pigs on a large scale. 

Thus, three different methods of attenuation had to be worked 
out for the first three bacterial vaccines developed in Pasteu/s 


laboratory: aging of the culture for chicken cholera, cultivation 
at high temperature for anthrax, and passage through rabbits for 
swine erysipelas. This achievement will appear little short of 
miraculous to anyone familiar with the technical problems in- 
volved. It is difficult to comprehend how Pasteur and his collabo- 
rators found it possible, in the course of three years, to work out 
the practical techniques of vaccination while still struggling to 
formulate the very concept of immunization. This is even the 
more startling in view of the fact that they continued at the same 
time to investigate the etiological problems of infection and were 
already engaged in the study of rabies. 

There is something odd in the selection by Pasteur of rabies as 
the next subject for his immunological studies. The disease was 
even then of relatively minor importance, claiming in France at 
most a few hundred deaths a year; the example of Germany and 
Australia had clearly shown that simple police and quarantine 
regulations for the control of dogs were sufficient to minimize its 
incidence still further. Moreover, there were no clues concerning 
its etiology; experimentation with it was laborious and expensive, 
and seemingly ill-adapted to the solution of theoretical and prac- 
tical problems. 

It has been claimed that Pasteur was attracted to the study of 
rabies through the vividness of childhood memories. He had never 
forgotten the impression of terror produced on him when a rabid 
wolf charged through the Jura, biting men and beasts on his way, 
and he had seen one of the victims cauterized with a red-hot 
iron at the blacksmith's shop near his father's house. The persons 
who had been bitten on the hands and head had succumbed to 
hydrophobia, some of them with horrible suffering; there were 
eight victims in the immediate neighborhood of Arbois and for 
years the whole region remained in dread of the mad wolf. 

It is possible that this experience of his youth may have influ- 
enced Pasteur's decision, but alone it could not have determined 
it. Rabies had long had a firm hold on public imagination and was 
the epitome of terror and mystery. It was therefore well suited 


to satisfy Pasteur's longing for romantic problems, as Renan 
hinted in his usual subtle manner during the speech welcoming 
Pasteur at the French Academy of Letters. "It is rabies which pre- 
occupies you today. You will conquer it and humanity will owe to 
you deliverance from a horrible disease and also from a sad 
anomaly: I mean the distrust which we cannot help mingling with 
the caresses of the animal in whom we see most of nature's smil- 
ing benevolence/ 3 Thus, rabies combined a supreme challenge to 
the experimenter and his method, an occasion to deal with one of 
the apparently inscrutable problems of nature, and the chance to 
capture the interest of the medical and lay public by a spectacular 
achievement. In fact, Pasteur was right in the selection of this 
seemingly hopeless problem. The Pouilly le Fort experiment had 
rendered the public conversant with the doctrine of immunization, 
but it was the prophylaxis of rabies which made of microbiologi- 
cal science an established religion, and surrounded its creator with 
the halo of sainthood. 

We have pointed out in a preceding chapter that experi- 
mentation with rabies demanded the development of entirely new 
methods. The incubation period of the disease was greatly short- 
ened and rendered more predictable by inoculating the infective 
matter directly into the nervous tissue. When the virus was passed 
through the brain of rabbits its virulence increased for these ani- 
mals and the incubation period became progressively shortened 
to six days. Pasteur referred to the virus so stabilized as "fixed 
virus." On the other hand, passage through a series of monkeys at- 
tenuated the virus for dogs, rabbits and guinea pigs. Thus it be- 
came almost as easy to experiment with rabies as with bacterial 
infections, even though nothing was known of the causative agent 
of the disease. Armed with these techniques, Pasteur was now 
ready to apply himself to the development of a vaccine. 

It is certain that many different schemes were imagined by 
Pasteur for the attenuation of the virus, but only the one upon 
which he settled is known to us. Fortunately, some of the circum- 
stances under which he arrived at the practical solution of his 
problem have recently been made public by Loir. Unknown to 


Pasteur, Roux was studying at the time the length of survival of 
the rabies virus in the spinal cord. For this purpose, he had placed 
infected cord in a flask with two openings, the cord hanging in- 
side and attached to the stopper which closed one of the openings. 
Pasteur once walked into the incubator where Roux's flasks had 
been placed, accompanied by Loir. 

"At the sight of this flask, Pasteur became so absorbed in his 
thoughts that I did not dare disturb him, and closed the door of 
the incubator behind us. After remaining silent and motionless 
a long time, Pasteur took the flask outside, looked at it, then re- 
turned it to its place without saying a word. 

"Once back in the main laboratory, he ordered me to obtain a 
number of similar flasks from the glass blower. The sight of Roux's 
flasks had given him the idea of keeping the spinal cord in a con- 
tainer with caustic potash to prevent putrefaction, and allowing 
penetration of oxygen to attenuate the virus. The famous portrait 
painted by Edelfeldt shows Pasteur absorbed in the contempla- 
tion of one of these flasks/* 

Thus was born the first technique of attenuation of the rabies 
virus. The method consisted in suspending in dry, sterile air the 
spinal cords of rabbits which had died from the injection of fixed 
virus. In the course of about two weeks, the cord became almost 
nonvirtdent By inoculating into dogs emulsions of progressively 
less attenuated cord, it was possible to protect the animal against 
inoculation with the most virulent form of virus. A dog receiving 
infected spinal cord dried for fourteen days, then the foEowing 
day material thirteen days old, and so on until fresh cord was 
used, did not contract rabies, and was found resistant when in- 
oculated in the brain with the strongest virus. In other words, 
it was possible to establish immunity against rabies in fifteen 

Under normal conditions of exposure, rabies develops slowly 
in man as well as in animals. For example, a man bitten by a mad 
dog ordinarily does not display symptoms of the disease until a 
month or more after the bite. This period of incubation therefore 
appeared long enough to suggest the possibility of establishing 


resistance by vaccinating even after the bite had been inflicted. 
Experiments made on dogs bitten by rabid animals, and then 
treated with the vaccine, gave promising results. Would the same 
method be applicable to human beings bitten by rabid animals 
and still in the incubation period of the disease? 

The story of the mental anguish which Pasteur experienced 
before daring to proceed from animal experiments to the treat- 
ment of the human disease has been often told. The thought of 
injecting into man rabid virus, even though attenuated, was ter- 
rifying. Furthermore, the procedure went counter to one of the 
medical concepts of the time, namely, that one could not deal 
with virus once it had become established within the animal 
body. It was bound, therefore, to stir up great and justified opposi- 
tion from conservative physicians. In fact, the opposition to the 
application of the rabies treatment to human beings did not come 
only from the medical world at large, but even from Pasteu/s 
own laboratory. Roux, in particular, felt that the method had not 
been sufficiently tested in animals to justify the risk of human 
trial and refused to sign with Pasteur the first report of treatment 
He ceased to participate in the rabies study and resumed his as- 
sociation with the laboratory only when Pasteur became the 
object of bitter attacks in the Academy of Medicine. 

The decision to apply rabies vaccination to man was forced 
upon Pasteur when a young boy, Joseph Meister, was brought to 
him for treatment. The physiologist Vulpian and the physician 
Grancher assured Pasteur that the nature of the bites made it 
likely that the boy would contract fatal rabies, and that the evi- 
dence derived from experimentation in dogs was sufficient to 
justify attempting the treatment. Grancher took the medical re- 
sponsibility of the case and from then on managed the program 
for the treatment of rabies in human beings under Pasteur's close 

Joseph Meister, aged nine, was brought from Alsace to Pasteur 
July 6, 1885, suffering from bites inflicted by a rabid dog on the 
hands, legs, and thighs. On July 7, sixty hours after the accident, 


the boy was injected with rabbit spinal cord attenuated by four- 
teen days' drying. In twelve successive inoculations he received 
stronger and stronger virus until on July 16 lie received an inocu- 
lation of virulent cord removed the da} 7 before from the body of a 
rabbit that had died following inoculation with fixed virus. Joseph 
Meister exhibited no symptoms and safely returned to Alsace. He 
later became gatekeeper of the Pasteur Institute. In 1940, fifty- 
five years after the accident that gave him a lasting place in medi- 
cal history, he committed suicide to escape being compelled to 
open for the German invaders the crypt where Pasteur is buried. 

The second case treated by Pasteur was that of Jean Baptiste 
Jupille, aged fifteen, a shepherd of Villers-Farlay in the Jura. 
Seeing a dog about to attack some children, Jupille seized his 
whip and attempted to drive it away, but was severely bitten; he 
finally managed to wind his whip around the muzzle of the animal 
and to crush its skull with his wooden shoe. The dog was subse- 
quently declared rabid, and Jupille was brought to Paris for treat- 
ment six days after being bitten. He survived, and his deed was 
commemorated in a statue which stands today in front of the 
Pasteur Institute in Paris. 

These two dramatic successes encouraged numerous patients 
to come to Pasteur for treatment after being bitten by animals 
known or presumed to be rabid. By October 1886, fifteen months 
after Joseph Meister had first been treated, no fewer than 2490 
persons had received the vaccine. Thus, like Jenner, Pasteur saw 
his method become an established practice within a short time of 
its inception, but as had been the case with smallpox vaccination, 
the rabies treatment was immediately attacked as valueless, and 
capable of causing the very disease which it was designed to con- 
trol. There are few physicians who now believe that either small- 
pox or rabies vaccination can be a likely source of danger to the 
patient when properly administered, but much question has been 
raised concerning the effectiveness of rabies treatment Before 
discussing this problem, however, it is necessary to retrace our 


steps somewhat and consider certain practical aspects of the dif- 
ferent methods of vaccination discovered in Pasteur's laboratory. 

As soon as he had worked out the technique of anthrax vaccina- 
tion, Pasteur expressed the desire for an opportunity to apply it 
to farm animals under field conditions. Anthrax was then a disease 
of great economic importance and the possibility of protecting 
against it constituted a lively subject of discussion in veterinary 
circles. The germ theory was still in its infancy and few were the 
physicians and veterinarians who had any concept of the scien- 
tific meaning of immunization. Among those who discussed the 
discovery, there were a handful who were dazzled by Pasteur's 
achievements, and many more who had only scorn for the odd 
claims of one whom they regarded as a conceited chemist, un- 
versed in true medical thinking. It is a fact not without interest 
that Rossignol, the man who took the initiative in organizing the 
first practical field test of immunization, in 1881, was one of the 
critics of the germ theory. One may well suspect that his avowed 
desire to serve the cause of truth was not unmixed with the hope 
that he would gain from the experiment the prestige of having 
been the champion of classical medicine at a time when it was 
threatened by the invasion of microbiological doctrines. In Janu- 
ary of the same year Rossignol had written in a sarcastic vein: 
"Microbiolatry is the fashion and reigns undisputed; it is a doc- 
trine which must not even be discussed, particularly when its 
pontiff, the learned M. Pasteur, has pronounced the sacramental 
words, I have spoken. The microbe alone is and shall be the char- 
acteristic of a disease; that much is understood and settled; hence- 
forth the germ theory must take precedence over the clinical art; 
the microbe alone is true, and Pasteur is its prophet" 

During the spring of 1881, Rossignol succeeded in enlisting the 
support of many farmers of the Brie district to finance a large- 
scale test of anthrax immunization. Pasteur was well aware of the 
fact that many veterinarians and physicians saw in the test a 
welcome occasion to cover the germ theory with ridicule; nothing 
could set in bolder relief, therefore, his confidence and gameness 


of spirit than his acceptance of the incredibly drastic terms of the 
protocol submitted to him. Rossignol publicized the program of 
the test widely and the experiment thus became an event of inter- 
national importance. It took place in the presence of a great as- 
sembly of people of all kinds, including the Paris correspondent 
of The Times of London, Mr. De Blowitz, who for a few days 
focused the eyes of his readers throughout the world on the small 
village of Pouilly le Fort. The following account is quoted from 
Roux, who participated actively in the preparation and execution 
of the experiment. 

"The Society of Agriculture of Melun had proposed to Pasteur 
a public trial of the new method. The program was arranged for 
April 28, 1881. Chamberland and I were away on vacation. Pas- 
teur wrote us to return immediately, and when we met him in the 
laboratory, he told us what had been agreed upon. Twenty-five 
sheep were to be vaccinated, and then inoculated with anthrax; 
at the same time twenty-five unvaccinated sheep would be inocu- 
lated as controls; the first group would resist; the second would 
die of anthrax. The terms were exacting, no allowance was made 
for contingencies. When we remarked that the program was 
severe, but that there was nothing to do except carry it out since 
he had agreed to it, Pasteur replied: *What succeeded with four- 
teen sheep in the laboratory will succeed with fifty in Melun/ 

"The animals were assembled at Pouilly le Fort, near Melun, 
on the property of M. Rossignol, a veterinarian who had origi- 
nated the idea of the experiment and who was to supervise it. 'Be 
sure not to make a mistake in the bottles,* said Pasteur gaily, 
when, on the fifth of May, we were leaving the laboratory in order 
to make the first inoculations with the vaccine. 

"A second vaccination was made on May 17, and every day 
Chamberland and I would go to visit the animals. On these re- 
peated journeys from Melun to Pouilly le Fort, many comments 
were overheard, which showed that belief in our success was not 
universal. Farmers, veterinarians, doctors, followed the experi- 
ment with active interest, some even with passion. In 1881, the 
science of microbes had scarcely any partisans; many thought 


that the new doctrines were pernicious, and rejoiced at seeing 
Pasteur and Ms followers drawn out of the laboratory to be con- 
founded in the broad daylight of a public experiment. They ex- 
pected to put an end with one blow to these innovations, so 
compromising to medicine, and again to find security in the sane 
traditions and ancient practices that had been threatened for a 

"In spite of all the excitement aroused by it, the experiment fol- 
lowed its course; the trial inoculations were made May 31, and an 
appointment was arranged for June 2 to determine the result. 
Twenty-five hours before the time decided upon, Pasteur, who 
had rushed into the public experiment with such perfect confi- 
dence, began to regret his audacity. His faith was shaken, as 
though he feared that the experimental method might betray him. 
His long mental tension had brought about this reaction which, 
however, did not last long. 3 The next day, more assured than ever, 
Pasteur went to verify the brilliant success which he had pre- 
dicted. In the multitude at Pouilly le Fort, that day, there were no 
longer any skeptics but only admirers." 

The experiment had consisted in the inoculation of twenty-four 
sheep, one goat and six cows, with five drops of a living attenu- 
ated culture o anthrax bacillus on May 5. On May 17, all these 
animals had been reinoculated with a culture less attenuated. On 

3 It lias been related that, on tlie day after the inoculation of the animals 
with the virulent challenge dose, a message was brought to Pasteur advising 
him that some of the vaccinated sheep appeared sick. Despite his confidence 
in the results of the laboratory experiments, he was under such great nervous 
tension that he immediately lost heart. Blinded by emotion, and refusing to 
consider the possibility that he had been mistaken, he turned to Roux who 
was present and accused him in violent words of having spoiled the field test 
by carelessness. As his wife was trying to quiet him down, pointing out that 
they had to start early the next morning for Pouilly le Fort, he replied that he 
could not expose himself to the sarcasm of the public and that Roux should 
go alone and suffer the humiliation since he was responsible for the failure, 

A telegram received during the night brought reassurance as to the prog- 
ress of the test; the next morning as Pasteur's group arrived at the railroad 
station, the enthusiastic welcome of the public gave them a forewarning of 
the complete success. Standing in his carriage, Pasteur turned to the crowd 
and exclaimed in a triumphant voice **Well, then! Men of little faith!** 
Biologie de I'lnvention, by Charles Nicolle. (Paris, Felix Alcan, 1932, p. 64) 


May SI all the immunized animals had been infected with a 
highly virulent anthrax culture, and the same culture had been 
Injected as well into twenty-nine normal animals: twenty-four 
sheep, one goat, and four cows. When Pasteur arrived on the field 
on the second day of June with his assistants Chamberland, Roux 
and Thuillier, he was greeted with loud acclamation. All the vac- 
cinated sheep were well. Twenty-one of the control sheep and 
the single goat were dead of anthrax, two other control sheep 
died in front of the spectators, and the last unprotected sheep 
died at the end of the day. The six vaccinated cows were well 
and showed no symptoms, whereas the four control cows had ex- 
tensive swellings at the site of inoculation and febrile reactions. 
On June 3, one of the vaccinated sheep died. It was pregnant and 
an autopsy suggested that it had succumbed on account of the 
death of the foetus but without showing any symptom of 
anthrax. Pasteur's triumph was thus complete. 

It has often been stated that the success of the Pouilly le Fort 
experiment was merely the result of tremendous luck, and that 
the chances of ever reproducing it are small. This is an error of 
fact, for similar experiments were repeated on several occasions 
and with equal success when carried out by Pasteur himself or 
done exactly according to his instructions. 

In July 1881 an experiment patterned after that of Pouilly le 
Fort took place at the Lambert farm near Chartres, with the only 
modification that, to render the test even more drastic and more 
convincing, the sheep were inoculated not with a broth culture 
of the anthrax bacillus, but with the blood of an animal dead of 
anthrax. The result was the same as that at Pouilly le Fort: abso- 
lute resistance of the vaccinated animals, and death of the 

In January 1882 and again in June 1882 Pasteur described the 
results of experiments in which the animals had been subjected to 
infection by contact and by feeding, under natural conditions of 
exposure; in these cases again, the protection of the vaccinated 
animals was absolute. Identical results were also obtained by 
workers outside of France, showing that wherever Pasteur's 


method of vaccination was faithfully applied and the challenging 
inf ectfon test carried out within the time which he prescribed, the 
animals were protected. 

There were, of course, some failures. Some, like the one re- 
ported from the veterinary school of Turin, were due merely to the 
fact that inexperienced workers had inoculated anthrax blood con- 
taminated with the vibrion septique. Despite the fact that such 
accidents were the object of long and bitter controversies, they 
taught nothing new and need not be considered further. More sig- 
nificant were the sarcastic criticisms of Robert Koch, who main- 
tained that, on account of the imperfection of Pasteur's techniques 
and because of the shortness of the immunity produced, anthrax 
vaccination was not a practical proposition. It is somewhat dis- 
heartening to see the great German bacteriologist attack Pasteur's 
discovery at the level of technical imperfections, without recog- 
nizing the immense theoretical importance and practical implica- 
tions of the new procedure. Nevertheless, some of Koch's criti- 
cisms were justified and deserve attention. 

Because of the pressure of work in Pasteur's laboratory, the 
preparation of the anthrax vaccine for wholesale distribution had 
been transferred to a small annex under Charnberland's super- 
vision. Unknown to Pasteur, Chamberland had taken the initia- 
tive of adding to each bottle of vaccine a small amount of culture 
of the hay bacillus (Bacillus subtilis}. When, by accident, Pas- 
teur became aware of this modification in his technique, he 
guessed that Chamberland's purpose had been to minimize any 
further attenuation of the vaccine by adding to it a microorganism 
capable of absorbing all available oxygen from the bottle, for 
Pasteur held steadfastly to the view that contact with oxygen was 
one of the most effective methods to bring about the attenuation 
of virulence. It is almost sure that the presence of the hay bacillus 
in the bottles of anthrax vaccine had been spotted in a German 
laboratory and that it accounted for Koch's scathing remarks 
concerning the purity of the vaccine. It is also possible that the 
culture of hay bacillus used by Chamberland may have exerted 
a toxic effect on the anthrax bacillus, causing its total or partial 


inactivation. TMs would have resulted in a weakening of tie vac- 
cinating potency and in some of the failures reported from the 
field. Of deeper significance were Koch's objections concerning 
the shortness of the immunity produced by the treatment. Pasteur 
soon became aware of this limitation, and he emphasized the 
necessity of repeating the vaccination every year, preferably in 
March before the natural disease became established. 

The complete success of Pasteur's own vaccination experiments 
was dependent upon an absolute respect for a number of minute 
technical details. The vaccines used had to be of the correct de- 
gree of attenuation; if too virulent, they could cause disease and 
even death in a number of animals; if too attenuated, they failed 
to establish an adequate degree of resistance. Moreover, the high 
level of resistance was usually short-lived, and in order to dupH- 
cate the Pouilly le Fort results, it was necessary to challenge the 
animals within a limited period of time after vaccination. Most 
experimenters failed to appreciate the importance of some of 
these details and attributed Pasteur's absolute success to luck. 
Like the experienced cook, the seasoned investigator often makes 
use in his work of a vast body of ill-defined but none the less real 
knowledge which never finds its way into the published descrip- 
tion of experimental procedures, Pasteur had this know-how of 
the experimental method to an extreme degree; he owed it to a 
complete mastery of the smallest details of his experimental world, 
and to an immense persistence in repeating endlessly the experi- 
ment which he was intent on perfecting. "Allow me," he once 
said to a group of students, "to give you the advice which I have 
attempted always to follow in my own work, namely remain as 
long as possible with the same subject. In everything, I believe, 
the secret of success is in prolonged efforts. Through perseverance 
in one field of investigation, one succeeds in acquiring what I 
am inclined to call the instinct of truth." 

As soon as he became convinced of the prophylactic efficacy of 
anthrax vaccination, Pasteur undertook to make himself the pro- 
moter of the new method. In order to convince those who wished 
to touch and to see before believing, he arranged for immuniza- 


tion experiments to be repeated in different places in France and 
abroad. To the secluded life in the laboratory where the studies 
on rabies had already begun, he now added a public life not less 
active, involving detailed analysis of the results of field experi- 
ments, replies to the demands for information, answers to the 
complaints, and defense in the face of criticism and sly attacks, 
as well as of open warfare. 

As early as 1882, less than two years after the discovery of the 
attenuation technique, Pasteur was in a position to report on the 
results obtained with 85,000 vaccinated animals. In 79,392 sheep, 
the mortality from anthrax had fallen from 9.01 per cent among 
uninoculated to 0.65 per cent among inoculated. Thanks to pro- 
digious efforts, anthrax vaccination soon became an established 
practice. By 1894, 3,400,000 sheep and 438,000 cattle had been 
vaccinated with respective mortalities of 1 and 0.3 per cent under 
natural conditions of field exposure. Just as the demonstration of 
the pathogenic role of the anthrax bacillus had been the touch- 
stone of the germ theory of disease, it was the vaccination against 
anthrax that revealed to the medical and lay mind the practical 
possibilities of the new science of immunity. 

Pasteu/s vaccination method involved two inoculations at inter- 
vals of twelve days with vaccines of very critical potency, the 
second being more virulent than the first; moreover vaccination 
had to be repeated every year in the spring to remain effective. 
This method is costly and consequently its use is restricted by 
economic factors, but these limitations do not in any way mini- 
mize the importance of Pasteur's achievement. He had demon- 
strated, once and for all, that immunization against infectious 
diseases was a possibility. Each microorganism, each type of in- 
fection, would present new problems to be solved within the 
framework of the factors conditioning the course and spread of 
the particular disease under consideration, but the faith that im- 
munity could be established against any infectious agent by arti- 
ficial means has never faltered since the days of Pouilly le Fort. 


Pasteur's next success was the immunization against swine ery- 
sipelas with a culture attenuated by passage through rabbits. 
Between 1886 and 1892, over 100,000 pigs were immunized in 
France, while the number exceeded 1,000,000 in Hungary from 
1889 to 1894. It is, however, the antirabies treatment which is 
usually quoted as Pasteur's greatest triumph and claim to im- 
mortality, and which established the hold of microbiological 
sciences on the practice of medicine. 

As early as October 1886, one year after the first application 
of the rabies treatment to Joseph Meister, Pasteur could report 
that there had been only ten failures out of 1726 bitten persons of 
French nationality who had been subjected to treatment by inocu- 
lation. Up to 1935, 51,107 patients had been inoculated in the 
Pasteur Institute of Paris, with 151 deaths, a mortality of only 
0.29 per cent These excellent results have been confirmed in all 
parts of the world. Yet, the application of the rabies treatment 
immediately became and remained for several years the subject of 
violent objections on the grounds that it was ineffective and more- 
over dangerous; Pasteur was accused of having infected patients 
with fatal rabies. These accusations are almost certainly unjusti- 
fied, although it is now known that the repeated injection of 
nerve tissue can, under certain circumstances, give rise to par- 
alytic symptoms which Pasteur's critics would have regarded as 
the effect of the rabies virus. On the other hand, opinion is still 
divided as to the effectiveness of Pasteur's antirabies immuniza- 
tion. Most epidemiologists believe that the treatment has saved 
far fewer lives than it was credited with at the time of its dis- 
covery; and some even doubt that it has any value at all because 
few of the human beings bitten by mad dogs ever develop 
rabies. The very existence of these startling views, similar to those 
reported earlier concerning smallpox vaccination, emphasizes the 
inadequacy of our knowledge concerning the natural history of 
infectious diseases. The technical reasons which account for this 
state of affairs cannot be discussed here, beyond restating that the 
existence of the many unrelated and uncontrollable factors which 
condition the spread and course of contagious diseases often 


makes it extremely difficult to evaluate convincingly the effect of 
prophylactic or therapeutic measures. 

Some tragic failures were recorded following the successful 
treatments of Meister and Jupile. On November 9, 1885, there 
was brought to Pasteur the little girl Louise Pelletier who had 
been bitten on the head by a mountain dog thirty-seven days be- 
fore. The nature of the wounds and the time elapsed since the 
bite convinced Pasteur that the treatment would almost certainly 
fail, and he knew that any failure would provide ammunition to 
the enemies of his method. Nevertheless, he could not resist the 
prayers of the child's parents, and against his better judgment he 
consented to treat her. The first symptoms of hydrophobia became 
apparent on November 27, eleven days after the end of the treat- 
ment, and Louise Pelletier died. She was the first casualty of the 
antirabies treatment, one which was often and unfairly played up 
by Pasteur's opponents. A few years later M. Pelletier made the 
following statement in a letter concerning the circumstances of 
his daughter's death: 

*Among great men whose life I am acquainted with ... I do 
not see any other capable of sacrificing, as in the case of our dear 
little girl, long years of work, of endangering a great fame, and of 
accepting willingly a painful failure, simply for humanity's 

As the number of patients applying for treatment increased, so 
naturally did the number of failures and the frequency of opposi- 
tion from physicians. Most, even among Pasteur's followers, held 
the view that the method was not adequately worked out for 
human application. Some even accused Pasteur and his collabo- 
rators of homicide by imprudence. Grancher, who performed the 
rabies inoculations and therefore had to bear much of the brunt 
of the fight, has described the atmosphere of hostility that sur- 
rounded the Pasteur camp: 

These same men, fervent disciples of Pasteur, hesitated 
to follow him on this new ground of antirabies treatment. 
I can still hear Tarnier speaking, as we walked out of those 
memorable meetings at the Academy of Medicine where 


Pasteur's adversaries accused Mm and his disciples of homi- 

"My dear friend/' Tamier told me? **it would be neces- 
sary to demonstrate, by repeated experiments, that you can 
cure a dog, even after intracraniai inoculation; that done, 
you would be left in peace." 

I replied that these experiments had been made; but 
Tamier did not find them numerous enough, and still he 
was one of Pasteur's friends. 

I felt disaffection and embarrassment grow all around us, 
not to speak of the anger which was brooding under cover, 
One day, I was at the Medical School for an examina- 
tion. ... I heard a furious voice shouting, "Yes, Pasteur is 
an assassin." I walked in, and saw a group of my colleagues, 
who dispersed in silence. 

And this was not Professor Peter, who had at least the 
courage of his opinion. And his opinion was as follows. 
"During the first ten months of the Pasteur treatment, the 
method was ineffective. Now that it has been modified, it 
has become outright dangerous. Pasteur confers on the per- 
sons whom he inoculates the hydrophobia of xabbits labo- 
ratory rabies/" 

These assertions were based upon the type of clinical 
symptoms exhibited by a few patients who had succumbed 
despite the treatment. In vain did we point out that rabies 
was not yet known in all the variety of its symptoms. In vain 
Vulpian would point to numerous facts of paralytic rabies 
reported before the advent of the treatment. Pasteur's adver- 
saries replied that paralytic rabies was transmitted to man 
by the injection of the spinal cord of animals dead of para- 
lytic rabies. . . . 

Certain political and medical journals as well as a number 
of politicians and the Antivivisectionist League conducted 
a violent campaign against Pasteur. Even in the colleges 
of Paris, students would split into Pasteurians and anti- 
Pasteurians and engage in fights. 

In the meantime, the laboratory was bending under the 
weight of the demands placed upon it. I was in charge of the 
inoculations and prepared the statistics with the help of 
Chantemesse and Charrin; Roux carried out the many tests 
required to establish the presence of rabies in biting dogs, 
and his activity, multiplied by the hard work of Viala, could 


hardly cope with this huge task. It was therefore quite im- 
possible to satisfy Tarnier's request and to take up again the 
experiments of vaccination of dogs after inoculation by the 
intracranial route. 

Furthermore, at this date of January 1887, there was no 
laboratory in Europe equipped to repeat Pasteur's experi- 

Pasteur's health had suffered from continuous exertion, from 
anxiety over the results of the antirabies treatment, and from these 
endless and bitter struggles. As he began to exhibit symptoms of 
cardiac deficiency, his doctors Villemin and Grancher persuaded 
him to leave Paris for the South at the end of November 1886, but 
the attacks against him and his method did not subside during his 
absence. A suit was threatened against the laboratory by the 
father of a young patient who had died after receiving the treat- 
ment. Medical testimony had been obtained that the child had 
died of the type of hydrophobia characteristic of the rabbit para- 
lytic disease, and that Pasteur and Grancher were therefore re- 
sponsible for it. It was at that critical time that Roux, who had 
been estranged from the laboratory and even avoided seeing 
Pasteur, had returned to share in the common danger and help 
weather the storm. 

This incident brought Roux into contact with a young doctor, 
Georges Clemenceau, who was to become a center of turmoil in 
French political life during the early part of the twentieth cen- 
tury, and to gain international fame as the '"Tiger" of France 
during World War I. Clemenceau was a physician whose life 
was torn between his medical interests, his free thinking and 
radical philosophy, and his passionate love of freedom. He had 
taken sides against the antirabies treatment and was exploiting 
the case mentioned above in the political press. His opposition to 
rabies inoculation probably originated from the fact that he was 
hostile to Pasteur's conservative views in politics and that, like 
most other leftist thinkers, he had favored the theory of sponta- 
neous generation. Half a century later, in January 1930, it was 
Roux who was selected to deliver before the Academy of 


Medicine the obituary speech after Clemencean's death. He re- 
lated that in March 1924 the aged Tiger had asked him to call at 
his apartment. "He questioned me at length on the nature of 
fermentation and on the role of microbes in the transformation of 
matter. . . . The next day, I received from him a special delivery 
letter asking for further information on the subject of fermenta- 
tion. Thus Clemenceau appeared to me as a philosopher, revising 
with full serenity Ms scientific view of the world in the twilight 
of his lif e/* 

As mentioned above, it is probably true that the antirabies 
treatment may bring about paralytic symptoms in a few cases, 
although these are not necessarily due to the active virus present 
in the vaccine. Fortunately, these accidents are extremely rare 
and it is almost certain therefore that the accusations directed 
against Pasteur on this score were unjustified. There was perhaps 
more ground for the attacks aimed at the efficacy of the treatment. 
Pasteur's statistics., which have been repeatedly confirmed, indi- 
cated that more than 99.5 per cent of the individuals bitten by 
rabid dogs fail to die of the disease if treated by his method. 
Judged in such terms, the therapeutic result appears remarkable, 
but in reality it is difficult to evaluate the significance of this figure 
because the chance of an exposed person's contracting rabies if 
left unvaccinated is unknown. It appears probable that man pos- 
sesses a high resistance to the rabies virus and that the chance of 
fatal infection is exceedingly small, so small indeed that proof of 
the utility of the treatment is difficult to obtain. The discussions 
held on this subject before the Paris Academy of Medicine in the 
1880's reveal that some French clinicians of the time held similar 
views. In an impassionate and able plea against the Pasteur treat- 
ment, the Parisian clinician Michel Peter stated his case in the 
following terms: 

Rabies in man is a rare disease, exceedingly rare; I have 
seen only two cases in the course of thirty-five years of hos- 
pital and private practice, and all my colleagues in hospitals 
in the city, as well as in the country, count in units and not 
in tens (let alone hundreds) the cases of human rabies 
which they have observed. In order to amplify the beneficial 


effects of bis method and to mask its failures, It is M. 
Pasteur's interest to believe that the annual mortality of 
rabies in France is higher than it really is. But these are not 
the interests of truth. 

Do you wish to know for example how many individuals 
have died of rabies in Dunkirk in a period of twenty-five 
years? Only one. And do you wish to know how many have 
died of it in this same city in one year, since the application 
of the Pasteur method? One died of rabies. 

It would be difficult to determine whether belief in the rarity 
of human rabies was then prevalent among physicians, or whether 
Peter was misrepresenting the situation to bolster his thesis. In 
any case, there cannot be any doubt that Pasteur had some jus- 
tification in not sharing his colleague's view of the rarity of the 
disease. He remembered well the rabid wolf in Arbois and the 
eight victims who had succumbed to hydrophobia following bites 
on the head and hands. Later the reading of official reports had 
confirmed the impression left on him by this childhood experience. 
An official inquiry had concluded that, of 320 cases studied, 40 
per cent had died after bites from rabid dogs. In another report 
from the Sanitary Department of the City of Paris, the mortality 
rate had been estimated at 16 per cent. Finally, at the very time 
that Joseph Meister was under Pasteur's care, five persons were 
bitten by a rabid dog near Paris, and every one of them had died 
of hydrophobia. It is of little surprise, therefore, that Pasteur and 
most of his contemporaries should have been overwhelmed by the 
low mortality of 0.5 per cent among humans receiving the anti- 
rabies treatment. 

The difficulty of evaluating quantitatively the prevalence and 
severity of rabies was well expressed by the English commission 
charged with the duty of investigating the validity of Pasteur's 
claims in 1888: 

(1) It is often difficult, and sometimes impossible, to as- 
certain whether the animals by which people were bitten, 
and which were believed to be rabid, were really so. They 
may have escaped, or may have been killed at once, or may 
have been observed by none but persons quite incompetent 
to judge of their condition. 


(2) The probability of hydrophobia occurring in persons 
bitten by dogs that were certainly rabid depends very much 
on the number and character of the bites; whether they are 
on the face or hands or other naked parts; or, if they have 
been inflicted on parts covered with clothes, their effects 
may depend on the texture of the clothes, and the extent to 
which they are torn; and, in all cases, the amount of bleeding 
from the wounds may affect the probability of absorption of 

(S) In all cases, the probability of infection from bites 
may be affected by speedy cauterizing or excision of the 
wounded parts, or by various washings, or other methods of 

(4) The bites of different species of animals, and even of 
different dogs, are, probably, for various reasons, unequally 
dangerous. Last year, at Deptford, five children were bitten 
by one dog and all died; in other cases, a dog is said to have 
bitten twenty persons of whom only one died. And it is cer- 
tain that the bites of rabid wolves, and probable that those 
of rabid cats, are far more dangerous than those of rabid 

The amount of uncertainty due to these and other causes 
may be expressed by the fact that the percentage of deaths 
among persons who have been bitten by dogs believed to 
have been rabid, and who have not been inoculated or other- 
wise treated, has been, in some groups of cases, estimated 
at the rate of only 5 per cent, in others at 60 per cent, and 
in others at various intermediate rates. The mortality from 
the bites of rabid wolves, also, has been, in different in- 
stances, estimated at from SO to 95 per cent. 

All students of rabies appear in agreement on a few points. 
The chance of an individual contracting the disease depends to a 
large extent upon the depth and location of the bite inflicted by 
the rabid animal, and the bite of a mad wolf is very likely to cause 
rabies. In our communities, most wolves are behind the gates of 
the zoos, and a young Louis Pasteur of today would have no 
chance of seeing that wild animal roaming about the countryside 
of Arbois. Uncontrolled and stray dogs also have become scarce; 
like modern man under normal circumstances, they lead a lazy 


and comfortable life. Fed on ground-up diets and on well-cooked 
bones, most of them have lost the habit, if not the profound in- 
stinct, of biting deeply into living flesh; ugly dogs, once common 
on lonely farms, are almost nonexistent today. The rabies virus, 
and the susceptibility of man to it, have probably not changed, 
but the social circumstances under which man encounters the 
virus may be sufficiently different to have altered somewhat the 
expected course of the disease since Pasteur studied it. 

Fortunately for Pasteur's peace of mind, his work on rabies was 
immediately investigated by the official English commission men- 
tioned above, which repeated the animal experiments in England 
and analyzed the results of the human treatment in Paris. Its 
report, issued in July 1888, confirmed Pasteur's experimental find- 
ings by stating: 

1. That the virus of rabies may certainly be obtained from 
the spinal cords of rabbits and other animals that have died 
of that disease. 

2. That, thus obtained, the virus may be transmitted by 
inoculation through a succession of animals, without any 
essential alteration in the nature, though there may be some 
modifications of the form of the disease produced by it. 

3. That, in transmission through rabbits, the disease is 
rendered more intense; both the period of incubation, and 
the duration of life after the appearance of symptoms of in- 
fection being shortened. 

4. That, in different cases, the disease may be manifested 
either in the form called dumb or paralytic rabies which is 
usual in rabbits; or in the furious form usual in dogs; or in 
forms intermediate between, or combining both of these, but 
that in all it is true rabies. 

5. That the period of incubation and the intensity of the 
symptoms may vary according to the method in which the 
virus is introduced, the age and strength of the animal, and 
some other circumstances; but, however variable in its 
intensity, the essential characters of the disease are still 

6. That animals may be protected from rabies by inocula- 
tions with material derived from spinal cords prepared after 
M. Pasteur's method. . . . 


The Commission also investigated Pasteur's clinical records in 
Paris and carried out a detailed inquiry in the homes of ninety 
patients who had received the antirabies treatment; while em- 
phasizing the difficulty of evaluating the normal fatality following 
bites by rabid animals, it expressed confidence in the value of 
Pasteur's results. 

Thus, the personal investigation of M. Pasteu/s cases by 
members of the Committee was, so far as it went, entirely 
satisfactory, and convinced them of the perfect accuracy of 
his records. . . . 

From the evidence of all these facts, we tiunk it certain 
that the inoculations practiced by M. Pasteur on persons 
bitten by rabid animals have prevented the occurrence of 
hydrophobia in a large proportion of those who, if they had 
not been so inoculated, would have died of that disease. And 
we believe that the value of his discovery will be found 
much greater than can be estimated by its present utility, 
for it shows that it may become possible to avert, by inocu- 
lation, even after infection, other diseases besides hydro- 
phobia. . . . 

Peter remained unimpressed by the report remarking face- 
tiously, "The most curious point in this story is that the Report 
of the English Commission does not conclude, as one might have 
expected, by recommending the establishment of a Pasteur In- 
stitute in London, but instead recommends, as a means of rabies 
prevention, a more rigorous enactment of police regulations on 

And, indeed, the English Commission was correct in its prac- 
tical conclusions as well as in its evaluation of the importance of 
Pasteur's work. Even granted that the antirabies treatment had 
saved the lives of a few human beings, this would have been only 
meager return for so much effort, and for so many animals sacri- 
ficed on the altar of man's welfare. The same result could have 
been obtained, at much lower cost, by the muzzling of dogs and 
by the training of their owners to keep them under control. It is 
on much broader issues that Pasteur's achievements must be 
judged. He had demonstrated the possibility of investigating by 


rigorous techniques the infectious diseases caused by invisible, 
noncuMvable viruses; he had shown that their pathogenic poten- 
tialities could be modified by various laboratory artifices; he had 
established beyond doubt that a solid immunity could be brought 
about without endangering the life or health of the vaccinated 
animals. Thanks to the rabies epic, men were to be immunized 
against yellow fever and several other widespread virus diseases; 
even more important, immunization had become recognized as 
a general law of nature. Its importance for the welfare of man 
and animals is today commonplace, but only the future will reveal 
its full significance in the realm of human economy. 

The acquisition of immunity to an invading parasite is, in many 
ways, one of the most extraordinary phenomena of life. Man and 
animals can become resistant to what would otherwise be fatal 
infective doses of the causative agents of many Infectious dis- 
eases, as a result of prior exposure to these agents; the Immunity 
is specific and it is lasting, sometimes for a few months, often for 
many years. What is the nature of this change that transforms 
selectively the behavior of a living being toward a small fragment 
of the Universe? 

Pasteur had a ready answer to this question, one that for a 
time he considered convincing because it presented analogies 
with some of his previous experiences. He had observed that each 
microorganism has exacting nutritional requirements, the anthrax 
bacillus growing well in neutralized urine, the chicken cholera 
organism in chicken broth. By analogy, he imagined that the 
sheep is susceptible to anthrax, and the dog not sensitive to the 
same disease, because the former animal provides an adequate 
growth medium for the specific bacillus, and the latter does not. 
Pasteur had ako recognized that the chicken cholera bacillus 
refused to multiply in a medium in which a culture of it had al- 
ready been grown. For similar reasons, he felt, microbial agents 
of disease refuse to grow in a body which they have previously 
invaded: this body, like the medium, has been depleted by the 
first invasion of some factor essential for growth. 


"One could imagine that cesium or rubidium are elements 
necessary for the life of the microbe under consideration, that 
there exists only a small amount of these elements in the tissues of 
the animal, and that this amount has been exhausted by a first 
growth of this microbe; this animal, then, will remain" refractory 
until its tissues have recuperated these elements. As they are 
scarce, a long time may elapse before recuperation is adequate/' 
This "exhaustion theory" was by no means new; it had been sug- 
gested by Tyndall and in particular by Auzias-Turenne almost 
two decades earlier. Pasteur himself soon recognized, however, 
that the theory was incompatible with some of the facts of im- 
munity and he quickly discarded it, as he was always ready to 
abandon concepts that were not fruitful of new discoveries. 

He then turned the argument around: "Many microbes appear 
to produce in the media where they grow substances that have 
the property of inhibiting their further development. Thus, one 
can consider that the life of the microbe, instead of removing or 
destroying certain essential components present in the body of 
animals, on the contrary adds new substances which could pre- 
vent or retard its later growth." This was not an idle speculation. 
He had tried in 1880 to separate such an inhibitory principle 
from cultures of the chicken cholera bacillus. Although this at- 
tempt had failed, he was eager to pursue the hypothesis further. 
"I believe, today, that the attempt should be repeated in the pres- 
ence of pure carbon dioxide, and I shall not fail to try it." This 
was late in 1885. The controversy on rabies vaccination was in- 
creasing in violence, and time was getting short. In 1888, Pasteur 
suffered a new attack of paralysis and had to abandon experi- 
mental work. Had he been able to work a few years longer, he 
would certainly have recognized that his new hypothesis did not 
yet fit the facts, although it was getting closer to the truth. There 
are indeed produced in the body, as a result of infection or of 
immunization, substances which may interfere with the develop- 
ment of the infective agent in the tissues; these substances, how- 
ever, are not produced by the microorganism but by the invaded 
body itself, as a response to the infectious process. Pasteur never 


engaged in the experimental analysis of tills "immune response** 
of the host, but he lived to see one of its greatest triumphs in the 
development of diphtheria antitoxin, an achievement to which his 
assistant Roux contributed much important work in the newly 
created Pasteur Institute. 

Pasteur believed that the protective effect of vaccination re- 
sulted from the multiplication of the attenuated cultures in the 
body, a view which has been amply confirmed. He had also sus- 
pected, however, that the immune reaction was not necessarily 
dependent upon the living processes of the parasites but might 
be directed against certain of their constituents or products. 
Should this prove to be the case, he felt, one might use for vac- 
cination these constituents or products of the microbial cell, in- 
stead of living attenuated cultures. Thus, after having discovered 
that culture filtrates of the chicken cholera bacillus contained a 
nonliving soluble toxin, he injected the culture filtrate into birds 
hoping to immunize them against the disease, but failed. 

Early in the course of the rabies work, he suspected that at- 
tenuation of the infected spinal cord did not consist in a change in 
the intrinsic virulence of the rabies virus, but was the result of 
progressive decrease in the number of living particles. "The pro- 
gressive increase in the length of incubation of the disease in- 
duced ... by our spinal cords desiccated in contact with air, is 
due to the decrease in quantity of rabies virus in these cords and 
not to a decrease in their virulence.'' This conclusion led him to a 
further hypothesis. He postulated that immunization might be due 
not to the living virus itself but to a nonliving substance which 
retained its immunizing power even after the virus had been 
killed by prolonged desiccation. In other words, he believed in 
the existence of "a vaccinating substance, associated with the 
rabies virus." Interestingly enough the first record of this ex- 
traordinary thought is dated from a meeting of the Academy of 
Letters as early as January 29, 1885. In the course of a discussion 
on the Dictionary of the Academy, Pasteur wrote the following 
note: "I am inclined to believe that the causative virus of rabies 
may be accompanied by a substance which can impregnate the 


nervous system and render it thereby unsuitable for the growth 
of the vims. Hence rabies immunity. If this is the case, the theory 
might be a general one; it would be a stupendous discovery." 
On August 20, 1888, at the end of his active scientific life, he re- 
ported preliminary experiments suggesting that antirabies im- 
munity could be induced in dogs by injecting infected spinal 
cord rendered noninfectious by heating for forty-eight hours at 
35 C. "The heated cord which had become noninfectious was 
still effective as a chemical vaccine." Indeed, he went so far as to 
state, "It will not be long before the chemical vaccine ... of 
rabies is known and utilized/* This aspect of Pasteur's work is 
never discussed in textbooks, and it appears worth while therefore 
to quote at length the views that he presented in 1888 in the first 
issue of the newly created Annales de TInstitut Pasteur. 

How could one explain without assuming the existence of 
the rabies vaccinating substance the fact that . . . two dogs 
each inoculated under the skin with the content of ten 
syringes of a very virulent virus , . . became at once resist- 
ant to rabies? How is it possible that the large amount of 
rabies virus introduced under the skin does not start multi- 
plying here and there in the nervous system if, at the same 
time, there were not introduced a substance reaching this 
system even faster, and placing it under conditions such that 
it is no longer capable of allowing the growth of the 
virus . . . ? 

Some will ask why inoculation by trephination always in- 
duces rabies, and never the refractory state. . . . The true 
difference between the two routes of inoculation appears 
to be that the inoculation under the dura mater permits the 
introduction of only very small amounts of virus and conse- 
quently of its vaccinating substance, amounts insufficient to 
induce the refractory state, whereas much larger amounts 
can be introduced under the skin. 

Only experienced immunologists can appreciate the visionary 
character of these statements that acquired their full significance 
only after fifty years of research in the virus field. It is possible 
that the mechanism of resistance to rabies perceived by Pasteur 
in the dim light of his time will become more obvious when his 


findings are interpreted with the help of modern knowledge. Ef- 
fective immunization with killed filtrable viruses, and demonstra- 
tion of the phenomenon of interference, are technical achieve- 
ments only of the past decade and there is an exciting atmosphere 
of archeological discovery in detecting their first expression in 
these hesitating statements of the founder of immunology. 

A few months later, in the last presentation of experimental 
work from his own laboratory before the Paris Academy of 
Sciences, Pasteur reported a few sketchy observations concerning 
the possible existence in anthrax blood of a vaccinating substance. 
He had injected repeatedly into rabbits the blood withdrawn from 
infected animals and heated at 45 C. for several days; although 
the heated blood was presumably free of living bacteria, it 
seemed to confer upon the animals a certain degree of immunity. 
The experiments had had to be interrupted in the fall of 1887 
because of Pasteur's ill-health. When he returned to Paris the 
following spring, he was a broken man, unable to pick up the 
tools. After having accepted every scientific challenge, having 
fought with, facts, men and infirmity, he finally had to give up. 

Despite the inconclusiveness of these last observations on the 
vaccinating substances of rabies and of anthrax, there is a great 
human beauty in the spectacle of Pasteur getting ready at the end 
of his life to start on a new intellectual adventure. Most of his 
popular scientific triumphs had been gained by demonstrating 
the participation of a vital principle in chemical and pathological 
processes; he had shown that fermentation, putrefaction and dis- 
ease were caused by living microbial agents; that immunity could 
be established with attenuated living germs of disease. Thanks 
to him, a new land had been discovered and was being con- 
quered; busy men were at work to settle and exploit it But the 
old explorer was on his way again, blazing new trails. Living 
microorganisms were the cause of disease as well as of immunity, 
but how and through what agencies did they perform these 
prodigious feats? The Sibylline thoughts on the vaccinating sub- 
stance of rabies, the crude observations on the immunizing power 
of heated anthrax blood, were gropings towards the new con- 


tinent where the chemical controls of disease and Immunity were 
hidden. There, Pasteur would have joined hands with his old 
opponents, Liebig and Claude Bernard. He had not, as they 
thought, forfeited the luminous and vigorous doctrine of modern 
physiology for some dusty and degenerate vitalistic philosophy. 
He had searched with curiosity and eagerness for the primary 
causes of natural phenomena and found them in living processes. 
But instead of submitting to Life, he had first learned to con- 
trol and domesticate her, and was now ready to extract from the 
living entrails the secret of her power. It Is only because human 
days are so short that he left his work unfinished. 


Mechanisms of Discoveries 

We want the creative faculty to imagine that which 
we know. 


FOR THE SAKE of convenience, we have presented Pasteur's scien- 
tific work as a series of separate problems. In reality, these prob- 
lems were never separated in his mind, their prosecution often 
overlapped in time, and he considered them as part of a whole, 
evolving one from the other. 

Within this fundamental unity, one can recognize two definite 
chronological sequences in the questions which Pasteur chose for 
study. On the one hand, as we have shown, his emphasis shifted 
toward the solution of practical problems, away from large theo- 
retical issues. True enough, he exhibited to the end the same acuity 
in relating experimental findings to questions of broad signifi- 
cance, but he found less and less time to develop those aspects of 
his discoveries which did not bear on practical matters of tech- 
nology or medicine. On the other hand, his work shows an evolu- 
tion from the physicochemical, through the chemical and bio- 
chemical, to the purely biological point of view. This is evident 
from the topics which he selected for investigation first molec- 
ular structure, then the physiological mechanisms of fermenta- 
tion, and finally the pathogenesis of infectious diseases. 

Pasteur attempted to rationalize this evolution by attributing 
it to a compelling inner logic which had led him inevitably from 
one subject to the next "Carried on, enchained should I say, 
by the almost inflexible logic of my studies, I have gone from 


investigations on crystallography and molecular chemistry to the 
study of microorganisms." 

The chronological sequence of Pasteur's studies gives credence 
to the view that they are linked in an orderly manner within a 
progressively developing conceptual scheme, and the theory that 
it was a compelling logic which led him from crystallography to 
disease has been widely accepted. In reality, Pasteur's own writ- 
ings provide evidence that the different aspects of his work did 
not stem one from the other, in a progressive and orderly man- 
ner, as would appear from the order of appearance of his major . 
publications. His greatest discoveries were the fruits of intuitive 
visions and they were published in the form of short preliminary 
notes long before experimental evidence was available to sub- 
stantiate them. 

The dates of first publication of Pasteur's most important 
achievements reveal that the essential steps in discovery occurred 
at the very beginning of each of the periods which he devoted 
to the different fields of research. It was in 1848 he was then 
twenty-six, and had just graduated from the Ecole Normale 
that he published his findings and views concerning the relations 
between the crystal morphology of organic substances and their 
ability to rotate the plane of polarized light. All his subsequent 
publications until 1857 are essentially elaborations of these views; 
the discovery made by the student at the Ecole Normale was the 
propelling force for ten years of research activity by the young 

In August 1857, shortly after having begun to work on fermen- 
tation, Pasteur presented in his preliminary paper on lactic acid 
a precise statement of the laws and methodology of a new science 
devoted to microorganisms and to the role they play in the 
economy of matter. Experimental evidence to substantiate these 
theoretical views kept him at work until 1875. 

A special phase of this problem, namely the existence of 
anaerobic life and its relation to the intimate mechanism of fer- 
mentation, first appears in his publications of 1860. But although 
the statement that "fermentation is life without oxygen" dates 


from February 1861, it was not until 1872 that Pasteur presented 
extensive discussion of its biochemical significance. 

The studies on spontaneous generation, on the manufacture of 
vinegar, wines, and beers, on the technique of pasteurization, 
which extend from 1860 to 1875, do not involve any new fun- 
damental concept and are merely developments of his earliest 
theoretical views on the germ theory of fermentation. 

The studies on silkworms illustrate in extreme degree Pasteur's 
successful use of Thunches" or intuition in the solution of scien- 
tific problems. Within two weeks after Ms arrival in Alais, he 
recommended the egg-selection method that was to lead to the 
practical control of pebrine. The four following years were de- 
voted to working out the practical details of the method, dem- 
onstrating its effectiveness, and elucidating the nature of the dis- 
ease. In this case, the different phases of the work followed in an 
order opposite to what might have been expected from a logical 

It was in 1877 that Pasteur published his first studies on animal 
pathology. Two years later, he recognized the possibility of im- 
munizing against chicken cholera, and, generalizing from this 
accidental observation, perceived its analogy with the procedure 
of vaccination against smallpox. From then on, he turned all his 
energies to the preparation of "vaccines" against various bacterial 
diseases, a pursuit occupying the balance of his scientific life. 

Pasteur achieved his most startling results through bold guesses 
which permitted him to reach the solution of a problem before 
undertaking its systematic experimental study. Because he was 
well trained in the philosophy of the experimental method, he 
recognized that these guesses were nothing more than working 
hypotheses, the validity of which had to be verified and dem- 
onstrated by critical scrutiny, and which became useful only to 
the extent that operational techniques could be evolved to de- 
velop and exploit their logical consequences. Interestingly enough, 
the urge to overcome objections and contradictions, to triumph 
over his opponents, became in many cases a powerful incentive 
to the systematic accumulation of the proofs necessary to sup- 


port theories that had first been affirmed without convincing evi- 
dence. In the work of Pasteur, logic is evident in the demon- 
stration and exploitation of Ms discoveries, rather than in their 
genesis. It is the phase of his work devoted to the development 
of his ideas which makes the bulk of his long papers, and which 
gives the impression of orderly logical progression. 

Pasteur's associates and contemporaries have emphasized his 
dreamy and intuitive nature; and Tyndall described his genius 
as a happy blending of intuition and demonstration. The use of 
intuition as a guide to discovery is perhaps a more common 
procedure than some exponents of the scientific method are in- 
clined to believe. An extreme interpretation of Francis Bacon's 
writings has led to the view that the accumulation of well- 
established facts is sufficient to the elaboration of scientific truth, 
that facts speak for themselves and become automatically trans- 
lated into general laws. It is indeed certain that the experimental 
method has a self-propelling force, and that many discoveries 
have been made by the routine and faithful application of its 
xules without an obvious use of hypotheses or intuition, but it 
is also true that scientific creation often involves the selection, 
from the wealth of amorphous data, of those facts which are rele- 
vant to a problem formulated in advance from abstract concepts. 

In this respect the progress of science depends to a large extent 
upon anticipatory ideas. These give rise to the working hypothe- 
sis that constitutes the imaginative component and one of the 
mainsprings of scientific discovery. Before addressing himself to 
nature for a definite answer from results of experiments, every 
investigator formulates tentative answers to his problem. The 
experiment serves two purposes., often independent one from 
the other: it allows the observation of new facts, hitherto either 
unsuspected, or not yet well defined; and it determines whether 
a working hypothesis fits the world of observable facts. The 
precision and the frequency with which hypotheses hit the tar- 
get of reality constitute a measure of the intuitive endowment 
of their author, Needless to say, successful guesses are not suffi- 


cient for the Instrumentation of discovery. The scientist most 
also be able to demonstrate the validity and to exploit the con- 
sequences of his intuitions if they are not to be stillborn. 

Only few of the great experimenters have described the mental 
processes by which they discovered new facts or formulated new 
generalizations. Some, it must be admitted, assure us that their 
method consists merely in the use of their eyes, their ears, and 
other physical senses to perceive and describe reality as it pre- 
sented itself to them. This view is illustrated in the picturesque 
words of the physiologist Francois Magendie: "I am a mere street 
scavenger of science. With hook in hand and basket on my back, 
I go about the streets of science collecting whatever I find." 
Others have told a very different story. They report how a period 
of intense preoccupation with a given problem was followed by 
a flash of inspiration often occurring under odd circumstances, 
away from the bench or the desk, in the course of which the solu- 
tion presented itself, ready-made, as emerging from some sub- 
conscious labor. Examples of inspired creations are common from 
the world of arts and letters, and many scientists, several of 
them Pasteur's contemporaries, have acknowledged a similar 
origin to their discoveries. 

In the course of an address on his seventieth birthday, Hehn- 
holtz thus described how his most important thoughts had come 
to him. "After previous investigation of the problem in all direc- 
tions . . . happy ideas come unexpectedly without effort, like 
an inspiration. . . . They have never come to me when ... I 
was at my working table. . . . They come . . . readily during 
the slow ascent of hills on a sunny day." 

According to William Thompson (Lord Kelvin), the idea of the 
mirror galvanometer occurred to him at a moment when he hap- 
pened to notice a reflection of light from his monocle. The theories 
of the structure of the atom and of the benzene ring were for- 
mulated by Kekule under the following circumstances. He had 
been visiting a friend in London and was riding home on the last 
bus. Falling into a revery, he saw atoms flitting before his eyes, 


two coupled together, with larger atoms seizing the smaller ones, 
then still larger atoms seizing three and even four smaller 
atoms, all whirling around in a bewildering dance, the larger 
atoms forming a row and dragging still smaller atoms at the end 
of the chain. Arriving home, he spent the night sketching pictures 
of the "structural theory." 

At the time of the discovery of the benzene ring theory, Kekule 
was working on a textbook. Turning from his desk toward the 
fireplace, he fell into a hypnotic state of mind, seeing the same 
atoms flitting again before his eyes, long rows of them assuming 
serpentine forms. All at once, one of the serpents seized his own 
tail * c and whirled mockingly before his eyes." Flashing awake at 
once, Kekule began writing the benzene ring theory. 

To the uninitiated, it appears even more remarkable that many 
mathematicians like Gauss, Poincare and Einstein have traced 
some of their greatest discoveries to a sudden illumination. Ein- 
stein said, in Physics and Reality: 

There is no inductive method which could lead to the 
fundamental concepts of physics. Failure to understand this 
fact constituted the basic philosophical error of so many 
investigators of the nineteenth century. . . . We now realize 
with special clarity, how much in error are those theorists 
who believe that theory comes inductively from expe- 
rience. . . . 

Even Clerk Maxwell, probably the most rigorous and logical 
scientific mind of the nineteenth century, has emphasized that 
purely imaginative mechanical models and analogies are often 
the precursors of mathematical abstractions. As is well known, 
Faraday evolved many of his discoveries from the mechanical 
concept of lines of forces; for twenty-five years, he used and elab- 
orated this model until the lines of forces became to him as real 
as matter, and he mentally constructed a model of the universe 
in such terms. Maxwell at first borrowed from Faraday a similar 
model of the electromagnetic field. True enough, he discarded 
its use after he had reached an adequate mathematical formula- 
tion of electromagnetism with its help, but he acknowledged his 


indebtedness to Faraday's mechanical concept and added: "For 
the sake of persons of different types of mind, scientific truth 
should be presented in different forms and should be regarded 
as equally scientific whether it appears in the robust form and 
vivid coloring of a physical illustration or in the tenuity and 
paleness of a symbolical expression." 

Elsewhere., Maxwell attempted to analyze Faraday's method of 
discovery and admitted the possibility of apprehending truth by 
approaches vastly different from those usually understood under 
the name of scientific method. He considered that reality might 
be perceived not only through clear intellectual steps leading to 
well-understood relationships, but also through the apprehension 
of phenomena and events as a whole, before any analytical 
process has revealed the nature and relations of their component 

Faraday's methods resembled those in which we begin 
with the whole and arrive at the parts by analysis, while 
the ordinary mathematical methods were founded on the 
principle of beginning with the parts and working up to 
the wholes by synthesis. . . . 

We are accustomed to consider the universe as made up 
of parts, and mathematicians usually begin by considering 
a single particle, and so on. This has generally been sup- 
posed the most natural method. To conceive of a particle, 
however, requires a process of abstraction, since all our per- 
ceptions are related to extended bodies, so that the idea 
that the all is in our consciousness at a given instant is per- 
haps as primitive an idea as that of any individual thing. 
Hence, there may be a mathematical method in which we 
move from the whole to the parts instead of from the parts 
to the whole. 

Is not this apprehension of the whole responsible in part for 
some of the mysterious processes of intuition that have so often 
been claimed by men of science? Was it not such a process which 
made Gauss reply, when asked how soon he expected to reach 
certain mathematical conclusions, "that he had them long ago, 
all he was worrying about was how to reach them"? 


In certain respects, Darwin used this unanalytical intuitive 
approach in formulating the theory o evolution based on nat- 
ural selection. He became convinced of the fact of organic evo- 
lution the variability of species during his short stay in the 
Galapagos Islands, and the hypothesis of natural selection came 
to him in a flash while reading Malthus's essay on population. 
Twenty years elapsed before he would publish his theory, a 
period devoted to the accumulation of the detailed body of facts 
required to bolster his preconceived views. 

"The imagination," he said, ^is one of the highest prerogatives 
of man. By this faculty he unites former images and ideas inde- 
pendently of the will, and thus creates brilliant and novel re- 
sults. . . .** The value of the products of imagination depends, 
of course, upon the number, accuracy, and clearness of the im- 
pressions on which they are based; it is also conditioned by the 
power of voluntarily combining these impressions, and by the 
judgment and taste used in selecting or rejecting involuntary 

The opposition to the Origin of Species came not only from 
churchmen and from those scientific quarters in which the fixity 
of species was then an unattackable dogma, but also from many 
who questioned the validity of Darwin's discovery because it 
had not been achieved by the Baconian method, and owed too 
much to imagination instead of depending solely upon objec- 
tivity and induction. This aspect of the opposition to Darwin 
strengthened Huxley's belief that the Baconian method was fruit- 
less as an instrument of discovery, and that imagination and 
hypothesis were the most powerful factors in the development of 

"Those who refuse to go beyond fact rarely get as far as fact; 
and anyone who has studied the history of science knows that 
almost every great step therein has been made by the anticipa- 
tion of nature; that is, by the invention of a hypothesis which, 
though verifiable, often had little foundation to start with; and 
not infrequently, in spite of a long career of usefulness, turned out 
to be wholly erroneous in the long run." Huxley came to feel that 


Bacon's "majestic eloquence and fervid vaticination 5 * were yet, 
for all practical results concerning discovery, **a magnificent 

Yet the great Chancellor probably never meant that the un- 
imaginative accumulation of facts is synonymous with science, 
but wanted only to affirm that imagination cannot function use- 
fully without the help of accurate facts. The mirror galvanometer, 
the formula of the benzene ring, the theory of evolution, had not 
been generated from nothing, as a product of "pure** imagina- 
tion; they were the fruits of an enormous growth of physical, 
chemical and biological knowledge that had been available to 
Thompson, Kekule or Darwin at the proper time for the formu- 
lation of a scientific synthesis. The few who reach the intuitive 
perception of truth must be preceded by the host of workers, 
most of them forgotten, whose role it has been to accumulate 
the facts that constitute the raw material of successful working 
hypotheses, of the intuitions of discovery. The immense waste- 
fulness of organic life, whicri demands that thousands of germs 
perish so that one may live, has its counterpart in the processes 
of intellectual life; many must run, so that one or a few may 
reacli the goaL 

Because every discovery, even that which appears at first sight 
the most original and intuitive, can always be shown to have roots 
deep in the past, certain students of the history of science believe 
that the role of the individual in the advancement of knowledge 
is in reality very small. To support their views, they point out 
that many discoveries have been made simultaneously in different 
places, by different individuals working independently and un- 
known to each other. 

Thus, the phenomenon of electromagnetic induction was dis- 
covered independently and almost simultaneously by Joseph 
Henry in America and by Michael Faraday in England. Similarly, 
the law of conservation of energy was suggested in 1844 by 
Grove in his essay "The Correlation of Forces"; it was implied 
in Faraday's equivalence of different forms of force in 1847; it 


was analyzed in clear terms by Helmholtz in Germany and by 
Joule in England. And before any of these, the French physicist 
Carnot, the Russian chemist Lomonosov and the German physi- 
cian Mayer had arrived at essentially the same conclusion. Ob- 
viously, this second law of thermodynamics was as much a prod- 
uct of the preoccupation of the age as it was an expression of 
the genius of the men who formulated it. The periodic table of 
the chemical elements provides another example in which the 
accumulation of chemical knowledge became sufficient at a cer- 
tain time to elicit in two independent workers, Lothar Meyer 
and Dmitrij Mendelejeff, the vision of an orderly relationship be- 
tween the properties of atoms. In a similar manner, Darwin and 
Wallace reached simultaneously the conclusion that species of 
living organisms have evolved one from the other. 

Further evidence that the progress of science depends less than 
is usually believed on the efforts and performance of the indi- 
vidual genius, is found in the fact that many important discov- 
eries have been made by men of very ordinary talents, simply 
because chance had made them, at the proper time and in the 
proper place and circumstances, recipients of a body of doc- 
trines, facts and techniques that rendered almost inevitable the 
recognition of an important phenomenon. It is surprising that 
some historian has not taken malicious pleasure in writing an 
anthology of "one discovery" scientists. Many exciting facts have 
been discovered as a result of loose thinking and unimaginative 
experimentation, and described in wrappings of empty words. 
One great discovery does not betoken a great scientist; science 
now and then selects insignificant standard bearers to display its 

For all these reasons, one cannot doubt that discovery is always 
an expression of the intellectual, social and economic pressure of 
the environment in which it is born. Nevertheless, each generation 
produces a few individuals who direct this pressure into meaning- 
ful channels and who discipline and harness the chaotic forces of 
their scientific age to create out of them the temples of knowl- 


edge. Science has her nouveaux riches, opportunists who exploit 
new fields of research opened by others,, or those who merely 
profit from a discovery made by accident But there are also in 
the kingdom of science visionary explorers, builders, statesmen 
and lawgivers. History demands that both groups be considered, 
for both play a part in the evolution of knowledge. However, it 
is only by studying the mental processes of the creators and men 
of vision that we can hope to decipher the mechanisms of dis- 
covery, and to understand the relation of our perception to the 
world of facts. Of all this, unfortunately, nothing is known; no 
one can predict who will formulate a new law or recognize a 
new fact, and there is as yet no recipe by which a scientific dis- 
covery can be made. Progress in the understanding of the intel- 
lectual factors involved will certainly be slow, for, like its literary 
and artistic counterparts, the process of scientific creation is a 
completely personal experience for which no technique of ob- 
servation has yet been devised. Moreover, out of false modesty, 
pride, lack of inclination or psychological insight, very few of 
the great discoverers have revealed their own mental processes; 
at the most, they have described methods of work but rarely 
their dreams, urges, struggles and visions. 

Pasteur made a few remarks concerning those of his qualities 
which played a part in the unfolding of his astonishing scientific 
performance. Besides his reference to the logic which "en- 
chained" him from one field of endeavor to another, he often men- 
tioned his use of preconceived ideas, from which he derived the 
stimulus for many experiments preconceived ideas which he 
was always willing to abandon when they did not fit the observed 
facts. He also emphasized his painstaking efforts in the laboratory, 
his patience, his persistence, his willingness to submit to the teach- 
ings of experiment even when they went counter to his theo- 
retical views. But in reality, these statements do not reach the 
core of the problem. They tell nothing of what made Pasteur 
and his peers in the Kingdom of Science different from their 
contemporaries who also formulated hypotheses, checked them 
by the experimental method, labored diligently and faithfully, 


and yet failed to leave their footprints on the sands of history. 
We can see the mechanics of Pasteur's workings, but their inward 
urge remains hidden to us. 

All those who saw Pasteur at work and in everyday life have 
emphasized how completely and exclusively he became engrossed 
in the problem at hand, and how great was his power of con- 
centration. Visitors were unwelcome, laboratory associates must 
be few and silent, not even the family dinner or home atmosphere 
could interrupt the preoccupations of the day. So as to possess 
more completely all the details of the work done in his laboratory, 
he would insist upon writing down himself all experimental pro- 
cedures and findings in the famous notebooks. When returning 
from some Academy meeting, he would go down to the animal 
quarters, tear from the cages the labels prepared by his collabo- 
rators, and make new ones in his own handwriting as if to Iden- 
tify his life more completely with the experiments. He had the 
ability, and the discipline, to focus all his physical and mental 
energies on a given target, and perhaps as a consequence he could 
recognize immediately all manner of small details pertaining to 
it. One gets the impression that the intense "field" of interest 
which he created attracted within his range all the facts large 
and small pertinent to the solution of the problem which was 
preoccupying him, 

With his nearsighted eye, he was capable of seeing much that 
escaped others, a quality which he had probably possessed from 
his early youth. One can recognize it in the portraits which he 
painted in his early teens, and years of disciplined effort had 
merely served to intensify the priceless attribute. 

His first scientific venture illustrates well his method of inves- 
tigation. It was, as reported earlier, by intense pondering over 
the relation of optical activity to crystal morphology that he had 
imagined seen with the mind's eye that the crystals of op- 
tically active tartaric acid might display morphological evidence 
of asymmetry. And it was because of his gift of observation that 
he actually saw on the crystals the small asymmetric facets which 
his predecessors had failed to notice. 

Pasteur and Pierre Bertin-Mourot 

Pasteur in his laboratory of the Ecole Normale, Reproduced from 
the Journal Illustre, March SO, 1884 


Pasteur remained throughout his life an immensely effective 
observer. He succeeded in differentiating the flacherie from the 
pebrine of silkworms because he had noticed and remembered 
that, during the 1865 season, certain broods of worms had as- 
cended the heather in a peculiarly sluggish manner. He was led to 
guess the role played by earthworms in the epidemiology of an- 
thrax by noticing their castings over the pits where animals had 
been buried. He gave a classical description of the symptoms of 
chicken cholera, and of the effects of its toxin. With his primitive 
microscopes and without staining techniques, he learned to dis- 
tinguish the different microbial forms and to recognize the bac- 
terial impurities correlated with faulty fermentations; lie pointed 
out that the morphology of yeast varies somewhat with its state 
of nutrition; he noticed that the microorganisms present in the 
wine deposits looked larger because they fixed some of the wine 
pigments. Within two weeks after his arrival in Alais, he had 
learned to recognize the microscopic corpuscles of pebrine; he 
saw and described bacterial spores in the intestine of silkworms 
affected by flacherie before anything was known of the nature 
and physiological importance of these bodies. He described in 
precise terms the capsule of pneumococci and became skillful in 
detecting infection of brain tissue with the rabies virus, even 
though, he had no knowledge of pathological anatomy. 

The hours which he spent in silence looking at the object of 
his studies were not only periods of meditation. They were like 
long exposure times, during which every small detail of the seg- 
ment of the world which he was contemplating became printed 
in his mind. Even more, they served to isolate, as it were, a sec- 
tion of the universe; and every component of it became organized 
with reference to his preoccupations. It was during these hours 
that were born between him and his experimental material those 
subtle but sure relations which blossomed into the intuitive 
preception of the "whole," characteristic of most of his discov- 

But power of observation does not suffice to explain Pasteur's 
scientific performance. For he knew how to integrate any rele- 


vant observation into liis conceptual schemes. So important was 
this peculiarity in the genesis of his discoveries that it appears 
worth while to recall one specific example, illustrating how con- 
crete facts found their place in the worlds which he was con- 
stantly imagining. 

In 1859, while observing under the microscope a drop of sugar 
solution undergoing butyric fermentation, Pasteur noticed that 
the microorganisms present in it became motionless at the edge 
of the drop, while those in its center remained actively motile. 
This accidental observation acted as a spark which fired the deep 
layers of his mind loaded with incessant questionings and pon- 
derings concerning the nature of the fermentation mechanism. 
He was convinced that alcoholic fermentation, as usually ob- 
served, was dependent on the life of yeast but he also knew that 
the production of alcohol out of sugar did not involve the par- 
ticipation of oxygen. This indicated that, under certain conditions, 
life could proceed without oxygen, a conclusion in conflict with 
the doctrine then universally accepted that oxygen was the very 
breath of life. When Pasteur saw the butyric organisms become 
motionless as they approached, the edge of the droplet he imme- 
diately imagined that they were inactivated by contact with the 
air. Indeed, experiment soon proved that they failed to multiply 
in aerated media, whereas they grew abundantly when oxygen 
was removed from the environment. In this case an apparently 
trivial fact found its place in Pasteur's meditations and led him 
to conclude that (a) life can exist without oxygen, (b) fermen- 
tations in general are metabolic reactions by which any cell can 
derive its energy from certain organic substances in the absence 
of oxygen, (c) the production of alcohol is only a particular case 
of the fermentation process and is the reaction by which yeast 
obtains energy under anaerobic conditions. All these extraordi- 
nary views, formulated as early as 1861, did not receive adequate 
experimental confirmation until 1872, when the studies on beer 
gave to Pasteur the occasion to establish their factual validity. 
Meditation on a general problem had been fertilized by an acci- 
dental observation and had given birth to a discovery; the sys- 


tematic experimentation which followed served only to nurture 
and guide into adult development this child bom of the myste- 
rious union. 

In many instances, discovery appears to have evolved from the 
fact that Pasteur had been made alert to the recognition of a 
phenomenon, because he was convinced a priori of its existence. 
Such was the genesis, as we have discussed in detail earlier, of 
the work on molecular asymmetry. Even more illustrative, per- 
haps, are the studies on the theory and practice of immunization. 
Much impressed by the facts that smallpox rarely occurs twice 
in the same individual and that one can protect against it by 
vaccination, Pasteur had formed very early the conviction that 
one should be able to immunize against other contagious dis- 
eases as well. It was this conviction which allowed him to grasp 
at once the significance of his accidental finding that birds inocu- 
lated with avirulent chicken cholera bacilli became resistant to 
inoculation with the fully virulent cultures. Because he had been 
anticipating such a fact, he postulated its analogy with Jenner's 
use of cowpox for vaccinating against smallpox, and extended the 
meaning of the word vaccination to include the new phenomenon. 
Discovery in this case was essentially the recognition of a natural 
law in the separate occurrence of two isolated facts which could 
be connected by the process of analogy. 

Pasteur made frequent use of analogy as a source of ideas for 
Ms investigations. The dimoiphic right- and left-handed quartz 
crystals served him as a model for the study of the optical activity 
of tartaric acids. In this case the analogy was only formal, since 
the optical activity of quartz resides in the crystal structure, 
whereas that of organic substances is a fundamental property of 
the molecule itself. Nevertheless it was sufficient to drive the 
first wedge into the analysis of the relation between asymmetry 
of molecular structure and optical activity. As he progressed 
in this study, Pasteur ceased thmking in terms of the quartz 
model, which was no longer useful in devising new experiments. 
Instead, he imagined that the organic molecule itself was an 
asymmetric body, and he tried to illustrate the concept of molec- 


ular asymmetry which could not yet be described in chemical 
terms by pointing out that the opposite members of asymmetric 
molecules bear to each other the same relation that the right hand 
bears to the left, each resembling the mirror image of the other. 
The case of rabies offers a striking example of analogy, which, 
although based on false premises, led to successful experiments. 
Studies on chicken cholera, anthrax, and swine erysipelas had 
revealed the existence of attenuated cultures of bacteria which 
were unable to cause progressive disease, but still capable of vac- 
cinating against the fully virulent organisms. Nothing was then 
known of the nature of the rabies virus and there was no evidence 
that it bore any relation to bacteria. Nevertheless, Pasteur at- 
tempted to attenuate it, as he had bacteria, and he found that 
the spinal cord infected with the virus lost most of its infective 
power during desiccation in the presence of air, while retaining 
its ability to immunize against the virulent disease. He soon 
realized, however, that despite its successful outcome his work 
had been built upon a false assumption. Desiccation had not 
caused a true diminution of the virulence of the rabies virus, but 
only a progressive decrease in the number of active virus par- 
ticles. Whereas attenuation of the chicken cholera and anthrax 
cultures was truly due to a change in properties of the bacteria, 
the decrease in virulence of the spinal cord infected with rabies 
was due to the fact that there was less active virus left, and not 
to a change in the properties of the surviving virus. Although the 
hypothesis was erroneous, it had led him to the recognition of 
new and important phenomena. 

In general, great investigators have left in writing only the ulti- 
mate form of their thoughts, polished by prolonged contact with 
the world of facts, and often with the world of men. It is because 
they reach us in this purified state that scientific concepts possess 
an awe-inspiring air of finality, which gives the illusion of a pon- 
tifical statement concerning the nature of things. Anyone inter- 
ested in the performance of the human mind out of mere curios- 
ity, or for scholarly pursuit welcomes the publication of the 


tentative and often crude sketches through which artists and writ- 
ers evolve the final expressions of their ideals. However, scientific 
workers now consider it unbecoming and compromising to reveal 
their gropings towards truth, the blundering way in which most 
of them, if not all, reach the tentative goal of their efforts. This 
modesty, or conceit, robs scientific operations of much human 
interest, prevents an adequate appreciation by the public of the 
relative character of scientific truth, and renders more difficult 
the elucidation of the mechanisms of discovery, by placing exclu- 
sive emphasis on the use of logic at the expense of creative imag- 
ination. The raw materials out of which science is made are not 
only the observations, experiments and calculations of scientists, 
but also their urges, dreams and follies. 

Loir has spoken of the fanciful mental constructions in which 
Pasteur indulged before undertaking a new problem. Of these 
scientific novels, only fragments remain. We have mentioned 
earlier the designing of equipment for submitting plant growth 
and chemical synthesis to the action of strong magnetic and elec- 
tric fields, or to light rays inverted by mirrors, in the hope of 
creating living chemical molecules or of altering the properties 
of living beings. These attempts had the quality of an alchemist* s 
quest and Pasteur acknowledged it "One has to be senseless 
to undertake the projects in which I am now engaged.** The begin- 
ning of the work on rabies seems to have been particularly fruit- 
ful in unwarranted hypothesis; bacteriologists will perhaps find 
entertainment in the account of one of Pasteur's early theories 
concerning the etiology of the disease. As will be remembered, 
he had isolated from the saliva of the first rabid child that he 
studied a virulent encapsulated microorganism now known as 
the pneumococcus. Before recognizing that this organism did not 
bear any relation to rabies, he constructed the theory that the 
period of incubation of the disease was the time required for the 
dissolution or destruction in the tissues of the capsule surround- 
ing the microorganism. Had this working hypothesis fitted the 
facts of rabies, it would have been, indeed, an exciting theory; 
but because it did not, scientific etiquette rules it bad taste to 


mention it in print And yet, the elucidation of the mental proc- 
esses involved in scientific discovery requires a knowledge of the 
hypotheses that miscarry, as well as of those which bear fruit 

Pasteur was well aware of the enormous role played by imag- 
ination in his scientific performance, and he repeatedly acknowl- 
edged it. He was, however, always eager to try to dissociate his 
dreams from reality, regarding the experimental method as a 
tool almost infallible in skilled and honest hands to weed out 
facts from fancy. Throughout his life he retained the ability to 
eliminate from his mind, once and for all, hypotheses which had 
proved incompatible with factual observations or experimental 

^Preconceived ideas are like searchlights which illumine the 
path of the experimenter and serve him as a guide to interrogate 
nature. They become a danger only if he transforms them into 
fixed ideas this is why I should like to see these profound words 
inscribed on the threshold of all the temples of science: "The 
greatest derangement of the mind is to believe in something be- 
cause one wishes it to be so.* . . . 

"The great art consists in devising decisive experiments, leaving 
no place to the imagination of the observer. Imagination is needed 
to give wings to thought at the beginning of experimental in- 
vestigations on any given subject. When, however, the time has 
come to conclude, and to interpret the facts derived from observa- 
tions, imagination must submit to the factual results of the experi- 

Indeed Pasteur's imagination was always rich, often undisci- 
plined, but the verification of his scientific concepts was so exact- 
ing and severe that he remains unsurpassed in the validity of his 
claims within the range of his experimental world. 

In addition to his long practice of the art of experimentation 
and to his knowledge of its illusions and pitfalls, Pasteur had an 
imperious need for some form of solid conviction that only clean- 
cut and incontrovertible facts could give him. He liked to admire 
and to believe in institutions, men and facts. He despised vague 
philosophical and political doctrines, because he was uncom- 


fortable in uncertainties. He loved the experimental method not 
so much because it revealed new philosophical outlooks on the 
Universe as because it could answer an unambiguous Yes or No 
to well-defined questions asked in unambiguous terms. Facing 
the skeptical Ernest Renan, who was receiving him at the 
Academic Frangaise, he spoke of "this marvelous experimental 
method, of which one can say, in truth, not that it is sufficient 
for every purpose, but that it rarely leads astray, and then only 
those who do not use it well. It eliminates certain facts, brings 
forth others, interrogates nature, compels it to reply and stops 
only when the mind is fully satisfied. The charm of our studies, 
the enchantment of science, is that, everywhere and always, we 
can give the justification of our principles and the proof of our 

At the end of his life, Pasteur expressed regret at having aban- 
doned his early studies on molecular structure. In this regret, 
there was perhaps the longing for the youthful days when the 
intoxication of discovery had first been revealed to him. There 
was also the faith, which he never gave up, that molecular asym- 
metry was in some way connected with the property of life; and 
to deal with the origin of life had certainly remained one of his 
haunting dreams. Beyond all that, however, was the fact that his 
early work was the symbol of all the problems which he had 
abandoned in his restless march forward. He bad left many 
studies unfinished, although it was within his power to bring 
them to a more advanced stage of development and perfection. 
As if apologizing to his contemporaries and to posterity, he 
claimed that he had been "enchained" to an inescapable, forward- 
moving logic. And indeed, there was a definite logic in the se- 
quence of his works; but this logic was not inescapable. His career 
might have followed many other courses, each one of them as 
logical, and as compatible with the science of his time and with 
the potentialities of his genius. 

It is impossible, and indeed preposterous, to attempt to recast 
a life in terms of what it would have been had circumstances en- 


couraged the expression of its potentialities in other channels of 
endeavor. Nevertheless, it may be of interest to consider some 
of the directions in which Pasteur could have directed his genius, 
if the pressure of other callings had not imposed upon him the 
tasks which assured his immortality. This is not Use-majeste, for 
we shall do little more than elaborate on tentative projects of 
research which he himself is known to have suggested, in the 
form of casual remarks, and which only the shortness of days 
prevented him from developing further. 

The fact that the rotation of the plane of polarized light by the 
solution of optically active organic substances is the greater, the 
larger the number of molecules encountered by the beam of 
light, convinced Pasteur that these organic molecules possess 
some sort of asymmetry. He found numerous analogies for this 
hypothesis, but the science of structural organic chemistry was 
not yet sufficiently developed to permit a definite explanation of 
the phenomenon. However, the interpretation of molecular asym- 
metry of organic compounds was provided within a few years 
after he abandoned experimental work on the problem by 
Couer's and Kekule's theory that the carbon atom has a normal 
valence of four. In 1874, van't Hoff in Holland and Le Bel in 
France proposed, simultaneously, the theory of arrangement of 
atoms in space now known as stereoisoinerism which pro- 
vided a simple chemical interpretation for Pasteur's findings. 
Thus, all the components required for the formulation of this 
new phase of chemical science, one of the greatest in its theo- 
retical implications and practical consequences, became available 
at a time when Pasteur's physical energy, scientific imagination 
and knowledge of physical chemistry were at their highest level. 
Stereoisomerism could have evolved from the logical unfolding 
of his own scientific efforts. 

Nor did he need to limit himself to the purely chemical con- 
sequences of his initial discovery. He had recognized that the 
left and right tartaric acids exhibited very different behavior 
toward living agents, and pointed out that tie difference in taste 
of left and right asparagine was only one of several biological 


differences between these two substances. Observation of the 
specific behavior of certain enzymes with reference to the optical 
activity of organic compounds was well within the range of 
chemical knowledge of the second part of the nineteenth century, 
and would have brought Pasteur to experimental grips with the 
problem on which he spent so much romantic imagination: the 
relation of asymmetry to living processes. 

Many different "logical sequences'* could have stemmed also 
from the germ theory of fermentation. Because of his thorough 
chemical training, Pasteur could have separated and studied, both 
bacteriologically and chemically, a large variety of microbial 
processes which remained obscure long after him. The subsequent 
studies by others on the cycles of carbon, nitrogen, phosphorus, 
sulfur, and so on, in nature and particularly in the soil, required 
no technical procedures or theoretical knowledge beyond that 
which he possessed or could master. The relation of microbes to 
soil fertility, and to the general economy of matter, could have 
furnished ample material for a logical development of his life. 

He abandoned early his spectacular studies on microbial nutri- 
tion, and it is only during the past two decades that microorgan- 
isms have again become tools of choice for the study of many 
nutritional problems. Yet, the discovery that carbohydrates, pro- 
teins, fats and minerals do not constitute the whole subject of the 
science of nutrition, and that vitamins are necessary components 
of a complete diet, could have come earlier, and more easily, had 
the lower forms of life, instead of animals, been used as test 
objects. It was within the logic of the germ theory to develop 
many theoretical aspects of the science of nutrition and many 
of its applications. Although Pasteur emphasized that the same 
fundamental metabolic reactions are common to all living things, 
he could have done much more to substantiate the doctrine of the 
biochemical unity of life, perhaps one of the most far-reaching 
concepts of modern times. 

Understanding of microbial metabolism led him to formulate 
rational directives for the manufacture of vinegar, wine and 
beer, and his work inspired the leaders of the Carlsberg brewery 


in Copenhagen to establish a laboratory devoted to the improve- 
ment of brewing technology. But there are many other industries 
in which microorganisms do or could play a role. As Pasteur re- 
peatedly emphasized, one can find in nature microorganisms 
adapted to the performance of almost any organic reaction and it 
is possible to domesticate microbial life just as plant and animal 
life have been domesticated in the course of civilization. In fact, 
Pasteur himself stated: "A day will come, I am convinced, when 
microorganisms will be utilized in certain industrial operations on 
account of their ability to attack organic matter." This prophecy 
has been fulfilled, and today organic acids, various solvents, vita- 
mins, drugs and enzymes are produced on an enormous scale by 
microbial processes all this a logical development of Pasteur's 

It is a remarkable fact that many of the advances in the under- 
standing of infectious diseases, which have occurred since Pasteur 
and Koch, have been made with techniques so simple, and often 
so empirical and so crude, that they could have come just as well 
out of the early bacteriological laboratories. For this reason, to 
list the possible lines of work which Pasteur could have elected 
to follow instead of devoting himself to the practical problems 
of vaccination, would be to review a large part of medical micro- 
biology. A few examples will suffice. 

Very early, he recognized that certain microorganisms com- 
monly present in soil can affect the anthrax bacillus in such a 
manner as to render it unable to establish disease in animals. He 
suggested immediately that this phenomenon might lend itself 
to therapeutic applications, that saprophytic organisms might 
someday be used to combat infectious agents. Despite his pro- 
phetic vision, however, he neglected to exploit the therapeutic 
possibility which he had recognized. Had lie chosen to follow 
this line of investigation, the techniques then available would 
have permitted the isolation from soil of the strains of Bacillus, 
Penicillium or Streptomyces which have since been shown to 
produce substances capable of inhibiting the anthrax bacillus 
both in the test tube and in the animal body. Chemical knowledge 


was then sufficiently developed to allow the purification of these 
therapeutic substances of microbial origin up to a point where 
they could be of some use in practice. Thus, bacteriotherapy 
might have been born in 1880. Better than any subsequent phase 
of Pasteur's work, it could have been, indeed, the logical synthe- 
sis of his training as a chemist and of his familiarity with sapro- 
fjhytic and pathogenic microorganisms. Instead, the exploitation 
of microorganisms as producers of therapeutic antimicrobial 
agents had to wait almost three fourths of a century before it 
became a practical reality. The fruit of Pasteur's logic ripened 
only when the land which he had explored was tilled by the bac- 
teriologists and chemists of the twentieth century. 

It is to immunity that Pasteur addressed himself as a method of 
control of infectious diseases. Although most of his work in this 
line dealt with the use of attenuated living vaccines for im- 
munization, he might have approached the problem from a dif- 
ferent angle. He had early recognized the importance of non- 
living soluble bacterial toxins in the production of disease, and 
he could have selected antitoxic immunity as a goal for his efforts. 
Immunity to the toxins of diphtheria and tetanus was achieved 
within his lif etime, by methods no different from those available 
to him. The treatment of diphtheria by antitoxic serum was a 
logical development of his discovery of the toxin of chicken 
cholera. He could have attempted also to immunize with killed 
bacilli, instead of using the living attenuated microorganisms, a 
step which was taken in 1889 by Salmon and Smith while he was 
still alive. This approach, it appears, would have been very con- 
genial to him for he must often have longed to escape from 
the uncertainties attendant upon the use of living biological ma- 
terial. The modern trend of utilizing, for immunization, substances 
separated from killed bacilli, and amenable to purification and 
standardization by chemical procedures, would have satisfied his 
eagerness for well-defined methods. And in reality, he anticipated 
this development when he discussed the "chemical vaccines'* for 
anthrax and for rabies, and saw in them the method of the future. 

Pasteur often emphasized the great importance of the environ- 


ment, of nutrition, and of the physiological and even psychologi- 
cal state of the patient, in deciding the outcome of the infectious 
process. Had the opportunity come for him to undertake again 
the study of silkworm diseases, he once said, he would have liked 
to investigate the factors which favor the general robustness of 
the worms, and thereby increase their resistance to infectious 
disease. This statement reveals the potential existence of yet 
another Pasteur, who would have focused the study of con- 
tagious disease toward the understanding of those physiological 
and biochemical factors which condition the course and outcome 
of infection. If circumstances had favored the manifestation of 
this aspect of his potential personality, instead of those traits 
which determined tie dedication of his life to microbiology, the 
science of infectious disease might today have a complexion far 
different from that under which we know it. A logic of Pasteur's 
life centered on physiological problems is just as plausible as that 
wldch resulted from the exclusive emphasis on the germ com- 
ponent of the theory of contagious disease. 

The fact that one can so readily conceive of many different 
logical unfoldings of Pasteur's work, all compatible with his en- 
dowments, his training, his imagination, and witih the environ- 
ment in which he lived, is perhaps the most eloquent and con- 
vincing index of the richness of his personality. True genius, 
according to Dr. Johnson, is a mind of large general powers, 
accidentally determined to some particular direction, ready for all 
things, but chosen by circumstances for one. Although the ex- 
istence of these multiple potentialities, only a few of which find 
expression during the life of any individual, is most obvious and 
overpowering in the case of outstanding creators, it is not peculiar 
to genius. It is a characteristic of all men, indeed of all living 
things, and Pasteur had even encountered it in the microbial 
world. The Mucor that he had studied could exist as a long fila- 
mentous mold on the surface of culture media, but it could also 
grow yeastlike when submerged in a sugar solution. Pasteur's 
own student Duclaux was the first to show that the metabolic 


equipment of microorganisms, their enzymatic make-up, is de- 
pendent upon the composition of the medium in which they live; 
the specific adaptation of the cell to the chemical environment 
by the production of appropriate enzymes is now known to be a 
phenomenon of universal occurrence. Each cell, each living being, 
has a multipotential biochemical personality, but the physico- 
chemical environment determines the one under which it mani- 
fests itself. In these terms, the dependence of the expression of 
individuality upon the environment appears as mere chemistry, of 
little relevance to human problems. And yet, just as the Mucor 
grows either as filamentous mold or as a yeast depending upon 
the impact of the environment upon it, similarly, there exists for 
each one of us the potentiality of revealing ourselves to the world 
as many different individuals, but circumstances allow us to live 
only one of the many lives that we could have lived. 

It is often by a trivial, even an accidental decision that we 
direct our activities into a certain channel, and thus determine 
which one of the potential expressions of our individuality will 
become manifest. Usually, we know nothing of the ultimate orien- 
tation or of the outlet toward which we travel, and the stream 
sweeps us to a formula of life from which there is no returning. 
There is drama in the thought that every time we make a choice, 
turn right instead of left, pronounce one word instead of another, 
we favor one of our potential beings at the expense of all the 
rest of our personality nay, we likely starve and smother to 
death something of us that could have continued to live and 
grow. Every decision is like a murder, and our march forward is 
over the stillborn bodies of all our possible selves that will never 
be. But such is the penalty of a productive life. For "Except a 
corn of wheat fall into the ground and die, it abideth alone: but 
if it die, it bringeth forth much fruit." 

Very often, Pasteur must have looked over his past and won- 
dered what his life would have yielded had he selected other 
hunting grounds in which to spend his energies and display his 
genius. He often returned in his conversations and writings to the 
problems of his youth, and lamented having abandoned them on 


the way a symbol of the tragedy of choice. He had been, he 
thought, "enchained" to an inescapable logic. But in reality, it 
was not logic that had enchained him. It was the strange com- 
pulsion, the almost insane urge, which makes the born inves- 
tigator become possessed and indeed hypnotized by the new 
problems arising out of his own observations. The logic that 
Pasteur followed was not inevitable, although he did not suc- 
ceed in escaping it He could have followed many other courses, 
as logical, as fruitful. Discoveries greater than pasteurization and 
vaccination could be attached to the memory of his adult years, 
had he elected to live some other of the many lives that were 
offered to him by the gods the drama in the life of every 
aspiring man. 


Beyond Experimental Science 

Faith is the substance of things hoped for, the evi- 
dence of things not seen. 


THERE was a time when meditation on the relation of man to 
nature, the expression of wonder or anguish at the splendor and 
mysteries of the universe, the discovery of objective facts concern- 
ing the physical world and the application of these facts to the 
welfare of man were all, equally, the privilege and duty of the 
inquiring soul. Until late in the eighteenth century, philosophy 
the love of wisdom embraced the whole field of knowledge and 
was concerned with all aspects of the physical and metaphysical 

This belief in the essential unity of mental processes survives 
in the custom of the French Academy of Letters TAcad&nie 
Frangaise of admitting within its membership men of many 
different callings churchmen, statesmen, soldiers, engineers, 
scientists who have contributed to the advancement of man- 
kind or to the glory of France. For, said Ernest Renan, "in a well 
organized society, all those who devote themselves to beautiful 
and good causes are collaborators; everything becomes great 
literature when it is done with talent. 3 * Pasteur was elected to the 
Academie Frangaise in 1882. His literary titles were few but he 
brought to the venerable institution his genius, "this common 
basis for the creation of beauty and truth, this divine flame that 
inspires science, literature and art.** Many circumstances made 
his formal reception an event of peculiar glamour. He was at that 


time the most famous representative of French chemistry and 
biology, and the atmosphere of legend ahready surrounded his 
name. Pasteur, symbol of the power of exact sciences, was tak- 
ing the seat of Ernest Littre, who had become the prophet of 
positivist philosophy and the advocate of the scientific approach 
to human affairs, particularly in sociology and history. Pasteur, 
the man of unbending convictions and fiery temperament, wor- 
shiper of the experimental method but believer in the teachings 
of the Roman Catholic Church, was to be welcomed into the 
Aeademie by the smiling and skeptical Ernest Renan linguist, 
philosopher, historian one who had written of Christ as a son 
of man, and of positive science as the religion of the future. 

In addition to his supreme intelligence, circumstances had 
placed Renan in a favored situation to act as the spokesman of 
the men of letters to the world of science. He had first intended 
to become a priest but had lost the Catholic faith when, after a 
"conscientious search for the historical basis of Christianity," 
he had become convinced of its "scientific impossibilities/* In 
1845, at the age of twenty-two, he left the Great Seminary of 
Saint Sulpice to study letters and philosophy. It was at that time 
that he met Marcellin Berthelot, then twenty years old, who was 
soon to become one of the founders of organic chemistry, and a 
convinced apostle of the role of exact sciences in human affairs. 
Won over to the scientific faith by the unlimited confidence of 
the young chemist, Renan learned to admire science for reveal- 
ing the beauty and interest of natural phenomena. In it he saw 
also the promise of intellectual freedom as well as of material 
wealth, and the hope that exact knowledge would "solve the great 
enigma . . . and reveal to man in a definite manner the sig- 
nificance of things." Not only could the universe be controlled 
and admired. The time had come at last when it could be under- 

Renan continued throughout his life a lively intellectual inter- 
course with Berthelot by means of an extensive correspondence. 
But the dogmatic attitude of the chemist was fundamentally in- 
compatible with Ms own temperament, always inclined as he was 


to doubt that truth was on one side only, and always willing to 
listen to the views of his opponents. At the College de France, 
where he was professor of Sanskrit, he became closely asso- 
ciated with Claude Bernard, who held the chair of experimental 
medicine. From him he learned that the great experimental prin- 
ciple is Doubt, not a sterile skepticism but rather a philosophi- 
cal doubt, which leaves freedom and initiative to the mind. 
'Whereas/* said Bernard, "the scholastic ... is proud, intolerant, 
and does not accept contradiction . . . , the experimenter, who 
is always in doubt and never believes that he has achieved abso- 
lute certainty, succeeds in becoming the master of phenomena, 
and in bringing nature under his power/' 

To Renan, the man with the skeptical smile and warm heart, 
who questioned the absolute validity of any system but was al- 
ways preoccupied with the thought of improving the world, noth- 
ing could be more attractive than this experimental method, based 
on doubt at every step and yet deriving its power of action from 
this very doubt. 

According to academic custom, Pasteur was expected to pro- 
nounce the eulogy of his predecessor Littre on taking possession 
of his seat at the Academie Frangaise. But he did more. He seized 
the opportunity to take issue with positivist philosophy by affirm- 
ing that the scientific method is applicable only where experi- 
mentation is possible, and that it cannot be of any use in the prob- 
lems involving emotions and religious faith. 

"Auguste Comte's i fundamental principle," said Pasteur, "is to 
eliminate all metaphysical questions concerning first and final 
causes, to attempt to account for all ideas and theories in terms 
of concrete facts, and to consider as valid and established only 
that which has been shown by experience. According to him . . . 
the conceptions of the human mind proceed through three stages: 
theological, metaphysical and scientific or positivist. . . . 

"M. Littre was all enthusiasm for this doctrine and for its 
author. I confess that I have come to a very different conclusion. 

1 Auguste Comte was the founder of positivist philosophy. 


The origin of tins conflict in our views probably results from tihte 
very nature of the studies which have occupied his life and those 
which have monopolized mine. 

"M. Littre's studies have dealt with history, philology, scientific 
and literary erudition. The subject matter of these studies is ex- 
clusively the past, to which nothing can be added and from which 
nothing can be removed. Its only tool is the method of observation 
which, in most cases, fails to give rigorous demonstrations. On 
the contrary, the very characteristic of the experimental method 
is to accept none but absolutely convincing demonstrations. . . . 

"Both of diem unfamiliar with the practice of experimentation, 
Comte and Littre . . - use the word "experience/ with the mean- 
ing which it has in the conversations of society, a meaning very 
different from that of the word 'experiment' in scientific language. 
In the former case, experience is merely the simple observation 
of things with the induction which concludes, more or less legiti- 
mately, from what has been to what could be* In contrast, the 
true experimental method aims at reaching a level of proof im- 
mune to any objection. 

The conditions and the daily results of the scientist's work 
lead his mind to identify the idea of progress with that of inven- 
tion. In order to evaluate positivist philosophy, therefore, my first 
thought was to search it for the evidence of invention, and I did 
not Said it One certainly cannot dignify as invention the so-called 
law of the three stages of the human mind, or the hierarchic clas- 
sification of sciences, views which are at best crude approxima- 
tions without much significance. Positivism, offering me no new 
idea, leaves me reserved and suspicious." 

As director of the Academic for the occasion, Renan had had 
the privilege of reading Pasteur's speech in advance of the meet- 
ing and took a malicious pleasure in opposing his own broad and 
subtle philosophy to the convictions of his new colleague. He did, 
of course, praise the intellectual beauty and importance of Pas- 
teur's achievements, and expressed much admiration for the 
strenuous and incessant labor required of those who attempt to 
decipher the secrets of nature. As he sat facing the sixty-year-old 


scientist, lie could read on his worn and wrinkled face the efforts 
which each discovery had cost him, the struggles with facts, with 
men, with their convictions and conventions, and even more, per- 
haps, with his own intellectual and moral weaknesses. Science is 
not the product of lofty meditations and genteel behavior, it is 
fertilized by heartbreaking toil and long vigils even if, only too 
often, those who harvest the fruit are but the laborers of the 
eleventh hour. "Nature is plebeian; she demands that one work; 
she prefers callused hands and will reveal herself only to those 
with careworn brows.'* 

But at the same time, Renan could not refrain from being some- 
what amused by Pasteur's assurance that he understood clearly 
the respective place of science and sentiment in the problems of 
human life. With ironical words, he suggested that, in philosophi- 
cal matters, hesitation and doubt are more often successful than 
overconfidence in apprehending reality and truth. 

"Truth, Sir, is a great coquette. She will not be won by too 
much passion. Indifference is often more successful with her. She 
escapes when apparently caught, but she yields readily if patiently 
waited for. She reveals herself when one is about to abandon the 
hope of possessing her; but she is inexorable when one affirms 
her, that is when one loves her with too much fervor." 

While admitting the power of the exact sciences, Renan em- 
phasized with consummate grace and persuasiveness that the 
experimental method does not constitute the only legitimate tech- 
nique for the acquisition of knowledge. Sociologists, historians, 
and even philosophers also make use of scientific judgment in 
their studies, and human feelings and behavior as well as reli- 
gious dogma are, like other areas of thought, amenable to scien- 
tific analysis. He pointed out that the scientific method in histori- 
cal matters consists in the discovery, identification and evaluation 
of texts. Although less simple and less directly convincing than the 
experimental method, historical criticism is also a worthy in- 
strument for the understanding and formulation of important 

"The human spirit would be far less developed without it; I 


dare say, indeed, that your exact sciences . . . would not have 
come into being if there did not exist near them a vigilant guard- 
ian to keep the world from being devoured by superstition and 
delivered defenseless to all the assertions of credulity." 

Renan might have also answered Pasteur's scornful remarks on 
the sciences of "observation" by noting that Galileo and Newton 
had founded much of modern physics while working on problems 
of astronomy where direct experimentation with the subject 
material is not possible. He could have pointed to the growth of 
other sciences, such as epidemiology or psychology, which are 
largely based on observation and for which experimentation can 
at best only provide oversimplified models. It is surprising that 
Pasteur, who so often upheld the place of the historical method 
in the study of exact sciences, should have been unable to recog- 
nize in historical criticism a legitimate technique for the evalua- 
tion of data pertaining to human relationships. He should have 
been aware that social problems, which, must be solved objec- 
tively by future generations, had first to be defined by what Renan 
called his "little conjectural sciences/' sociology and history. 

Like Pasteur, Berthelot doubted that sociologists would ever 
contribute anything of practical importance to human welfare, 
but he based his skepticism on very different reasons. He had 
such unlimited confidence in the power of physicochemical sci- 
ences that he saw in them the eventual solution of all human 
problems. For him, the problems of life were mere extrapolations 
of problems of matter, and demanded no special methods for 
their elucidation. Pasteur, on the contrary, saw a profound schism 
between the world of matter and those vast areas where emotions 
and feelings rule the affairs of mankind. "In each one of us there 
are two men: the scientist who ... by observation, experimen- 
tation and reasoning, attempts at reaching a knowledge of nature; 
but also the sensitive man, the man of tradition, faith and doubt, 
the man of sentiment, the man who laments for his children who 
are no more; who cannot, alas! prove that he will see them again, 
but believes and hopes it, who does not want to die like a vibrio, 


who wants to be convinced that the strength which is in him will 
not be wasted and will find another life." 

Speaking in 1874 at the graduation exercises of the College of 
Arbois, where he had been a student, he affirmed that religious 
convictions are founded on the impregnable rock of direct per- 
sonal experience. "The man of faith . . . believes in a super- 
natural revelation. If you tell me that this is incompatible with 
human reason I shall agree with you, but it is still more impos- 
sible to believe that reason has the power to deal with the prob- 
lems of origins and ends. Furthermore, reason is not all . . . ; the 
eternal strength of the man of faith lies in the fact that the teach- 
ings of his creed are in harmony with the callings of the heart. . . . 
Who, by the deathbed of a beloved one, does not hear an inner 
voice assuring him that the soul is immortal? To say with the 
materialist 'Death is the end of all* is to insult the human heart.** 

At the time of his reception in the Academic Frangaise, he at- 
tempted to present a more intellectual justification of religious 
faith. According to him, positivism, while pretending to explain 
human behavior in scientific terms, fails to take into account the 
most important of all the positivist notions, that of infinity. Al- 
though an inescapable conclusion of human thinking, the notion 
of infinity is incomprehensible to human reason. Indeed, Pasteur 
felt, it is more incompatible with it than are all the miracles of 

"I see everywhere in the world the inevitable expression of the 
concept of infinity. It establishes in the depth of our hearts a belief 
in the supernatural. The idea of God is nothing more than one 
form of the idea of infinity. So long as the mystery of the infinite 
weighs on the human mind, so long will temples be raised to the 
cult of the infinite, whether God be called Brahma, Allah, Jehovah 
or Jesus." 

Replying to Pasteur, Renan pointed out that such statements 
gave a certificate of credibility to many strange tales. He was 
ready to grant that, in the field of the ideal, where nothing can be 
proved, all forms of belief and faith are justified. But miracles are 
specific claims that certain events have occurred, at definite times 


and places. They are, therefore, subject to historical criticism; 
and Renan failed to find substantiating evidence for any of the 
particular facts of religious history that had been thoroughly in- 
vestigated. It was not, however, on the miracles peculiar to each 
religious lore that Pasteur had based his criticism of positivist 
philosophy. He had merely claimed that the notion of infinity con- 
ditions human behavior, and has immense consequences in the 
life of societies. Auguste Comte and his followers had failed to 
recognize these deep and mysterious sources of inspiration 
through which the notion of infinity expresses itself in the hearts 
of men. Pasteur saw in them the spiritual link of humanity and 
the origin of man's nobility. 

"The Greeks understood the mysterious power of the hidden 
side of things. They bequeathed to us one of the most beautiful 
words in our language the word 'enthusiasm' En theos an 
Inner God. 

"The grandeur of human actions is measured by the inspiration 
from which they spring. Happy is he who bears within himself a 
god, an ideal of beauty, and who obeys it; ideal of art, of science, 
of patriotism, of the virtues symbolized in the Gospel. These are 
the living sources of great thoughts and great acts. All are lighted 
by reflection from the infinite/' 

Pasteur's opponents have seen an evidence of the philosophical 
limitation of his mind in this unwillingness to accept the possibil- 
ity that human emotions and religious faith could be amenable 
to scientific scrutiny. They have also regarded his attitude as an 
intellectual surrender due to his acceptance of the Catholic dis- 
cipline. Before accepting this interpretation, it is well to remem- 
ber that many of the greatest scientific minds of the nineteenth 
century Davy, Faraday, Joule, Maxwell, Lord Kelvin, Helm- 
holtz to mention only a few of the masters of exact sciences in 
non-Catholic countries have, like Pasteur, forcefully acknowl- 
edged their allegiance to the Christian faith and have dissociated 
their beliefs as men of sentiment from their behavior as experi- 
mental scientists, In the course of a lecture before the Royal In- 


stitution, Faraday once stated in words not very different from 
those often used by Pasteur that the concept of God came to his 
mind through channels as certain as those which led him to truths 
of physical order. 

Many scientific workers possess the ability to follow two inde- 
pendent and apparently conflicting lines of thought: on the one 
hand, the acceptance of religious dogmas, on the other, an abso- 
lute confidence in the ability of experimental science to analyze 
and control the mechanisms of the physical world. This attitude 
is symbolized by Newton, who formulated the mechanical laws 
ruling over the operations of the universe while retaining faith in 
the existence and power of a Creator who first put those forces 
into motion. The divorce between Christian faith and positive 
science became most widespread among the French scientific 
philosophers of the eighteenth century, but it is certain that they 
arrived at intellectual agnosticism or atheism, not through the 
examination of scientific knowledge, but by the way of philoso- 
phy. As physicists, they accepted Newton's gravitational force; as 
philosophers, they saw no need of his hypothesis concerning the 
existence of God. They converted Newtonian science into a me- 
chanical philosophy in which the past and the future were theo- 
retically calculable and man was a mere machine. They did not 
heed Newton's caution that the cause or nature of the gravita- 
tional force was unknown, that his law described only the rela- 
tions between bodies, not the ultimate nature of these bodies nor 
the forces that acted upon them. 

In contrast to their French contemporaries many British phi- 
losophers and scientific workers arrived at the conviction that the 
ultimate truths of nature transcend human understanding and 
that the most man can hope is to recognize and describe the rela- 
tionships between objects and events. While intellectually a de- 
featist philosophy, this point of view is a source of great effective 
power. It does not weaken man's conviction that he can learn 
through experience to control nature and use it for his own ends, 
and it directs his efforts towards objective and practical achieve- 
ments instead of speculative problems. Thus most scientists came 


to dismiss from their conscious minds, if not from their subcon- 
scious, the pretense that they were about to come to grips with 
the ultimate nature of reality. But they retained the hope, or care- 
fully nursed the illusion, that their efforts would help improve the 
lot of man on earth. Should even that satisfaction fail them, there 
remained, as alluring as ever, the enjoyment of search and the 
intoxication of discovery, and in this they found sufficient induce- 
ment to make of experimental science the dominating force of 
Western society. 

The dissociation between religious faith and experimental 
science received philosophical sanction and dignity from Im- 
manuel Kant. He assured the world that all matters concerning 
which no information can be obtained through the direct experi- 
ence of the senses the ultimate nature of the universe, the soul 
and God fall outside the range of rational knowledge. We can 
maintain neither their existence nor their nonexistence, and we 
are therefore justified in continuing to believe without need of 
proof in the existence of God and in the immortality of the soul. 

Kant's philosophy had a great appeal for many scientists. It 
absolved them from having to deal with the philosophical sig- 
nificance of reality, encouraged them to devote their efforts to 
tasks of practical importance and, by making all fundamental 
creeds immune from the attacks of science, it permitted them to 
retain their religious beliefs. The acceptance of Kant's philosophy 
explains how so many of the greatest experimentalists of the nine- 
teenth century found it possible to follow positive science and 
religious faith simultaneously. They felt free to suspend judgment 
on the interrelationships between the two on the ground that 
there was not as yet, and perhaps never could be, any objective 
evidence to permit understanding of their deeper implications. 

It is probable that the practice of this double standard by men 
such as Faraday, Maxwell, Helmholtz, Pasteur, appeared intellec- 
tually dishonest to those who had accepted what they considered 
the inevitable logical consequences of the scientific point of view, 
and who were willing to disavow any form of allegiance to Biblical 
teaching. In England, this attitude was proudly upheld by Tyn- 


dall, when he stated in his Belfast address: "We claim, and we 
shall wrest from theology, the entire domain of cosmological 
theory ." In France, the extreme form of the materialist faith was 
expressed by Berthelot in the astonishing statement: "The world, 
today, has no longer any mystery for us." 

Pasteur was far too conscientious and earnest to reject scien- 
tific materialism merely on the basis of emotions on the longings 
of his heart or the appeal to him of the notion of infinity. He ex- 
amined the question time and time again, attempting to restate, 
in terms of his scientific experience, those problems which have 
always compelled the thoughts of man and which so many phi- 
losophies and religions have sought to answer. It was particularly 
at the time of the controversy on spontaneous generation that he 
found it necessary to formulate, for himself, an opinion concern- 
ing the ability of experimental science to decipher the riddle of 
life. He reached the conclusion, as Claude Bernard had, that the 
mystery of lif e resides not in the manifestations of vital processes 
all of which pertain to ordinary physicochemical reactions 
but in the predetermined specific characters of the organisms 
which are transmitted through the ovum, through what he called 
the "germ/' 

"The mystery of life does not reside in its manifestations in 
adult beings, but rather and solely in the existence of the germ 
and of its becoming. . . . 

"Life is the germ with its becoming, and the germ is life. . . . 

"Once the germ exists, it needs only inanimate substances and 
proper conditions of temperature to obey the laws of its develop- 
ment ... it will then grow and manifest all the phenomena that 
we call 'vital,' but these are only physical and chemical phe- 
nomena; it is only the law of their succession which constitutes 
the unknown of life. . . . 

"This is why the problem of spontaneous generation is all- 
absorbing, and all-important. It is the very problem of life and of 
its origin. To bring about spontaneous generation would be to 
create a germ. It would be creating life; it would be to solve the 


problem of its origin. It would mean to go from matter to life 
through conditions of environment and of matter. 

"God as author of life would then no longer be needed. Matter 
would replace Him. God would need be invoked only as author of 
the motions of the world in the Universe/* 

Like an obsession, there recurs time and time again through his 
writings, often in unpublished fragments, the statement that "Life 
is the germ and its becoming." The concept of "becoming" was 
obviously borrowed., perhaps unknown to Pasteur, from the 
Werden of the Hegelian doctrine. This taught a logical or dia- 
lectic development of things according to which the whole world 

spiritual phenomena, man, together with all natural objects 
was the unfolding of an act of thought on the part of a creative 
mind. There is some irony in seeing the great French patriot and 
champion of the power of the experimental method, struggling to 
express his philosophical view of life in the words of the German 
archenemy of the experimental scientists. 

Pasteur was unquestionably sincere in affirming his willingness 

nay, his eagerness to believe in the spontaneous generation 
of life provided adequate proof was brought forward to demon- 
strate its occurrence. His religious faith was independent of scien- 
tific knowledge. Well aware of the limitations of the experimental 
method, he knew that his work had not proved that the genera- 
tion of lif e de novo was impossible, and that he had done nothing 
more than show the fallacy of all known claims. "I do not pretend 
to establish that spontaneous generation does not occur. One can- 
not prove the negative." But by the same token he protested the 
assumption, for which no evidence is yet available, that spon- 
taneous generation had been the origin of life in the universe. 

"I have been looking for spontaneous generation during twenty 
years without discovering it. No, I do not judge it impossible. But 
what allows you to make it the origin of life? You place matter 
before life, and you decide that matter has existed for all eternity. 
How do you know that the incessant progress of science will not 
compel scientists ... to consider that life has existed during 
eternity and not matter? You pass from matter to life because 


your intelligence of today . . , cannot conceive tilings otherwise. 
How do you know that in 10,000 years one will not consider it 
more likely that matter has emerged from life . . . ?" 

Pasteur never published these remarks, written in 1878. He may 
have reserved them for some ulterior communication, since other 
posthumous fragments suggest that he had intended to return to 
the problem of spontaneous generation, a project he did not ful- 
fill. Despite his conviction and self-assurance, he may have also 
feared the opposition that these unorthodox views would en- 
counter in the scientific world. In reality, however, he was not 
alone in questioning the order of the relation of life to matter. 
At about the same time Fechner in Germany pointed out that 
everywhere the living generates not only the living, but also, and 
much more frequently, the inanimate, although we never see life 
develop de novo out of inorganic matter. Preyer also asked him- 
self whether, instead of the living being evolved from dead mat- 
ter, it is not the latter which is a product of the former. Contrary 
to common sense as these views appear, they foreshadowed some 
of the modern developments of the theory of knowledge. Com- 
mon-sense realism gives us only a very limited view of the world. 
Our preceptions are no more than plane sections of the universe, 
from which we construct models of it to fit our practical needs 
and to help ourselves recognize some qualitative and quantitative 
relations between its component parts. But perceptions, and the 
models we derive from them, give us little if any understanding 
of the intrinsic nature of reality. The concepts of 'life" and of 
"matter" probably correspond to two of these abstract models, 
and the human mind has not yet succeeded in tracing significant 
relationships between them. 

If Pasteur saw no hope that the experimental method would 
ever reveal the origins and ends of the universe it was because he 
believed that "in good science, the word 'cause' should be reserved 
for the primary divine impulse which gave birth to the universe. 
We can observe nothing but correlations. It is only by stretching 
the true meaning of words unjustifiably that we speak of a cause 


and effect relationship when referring to one phenomenon which 
follows another in time and cannot occur without it." In much the 
same vein, Claude Bernard had also written: "The obscure con- 
cept of cause . . . has meaning only with reference to the origin 
of the universe ... in science it must yield to the concept of 
relation or conditions. Determinism establishes the conditions of 
phenomena and permits us to predict their occurrence and even 
under certain conditions to provoke it. Determinism does not give 
us any account of nature, but renders us master of it. ... Al- 
though we may think, or rather feel, that there is a truth which 
goes beyond our scientific caution, we are compelled to limit our- 
selves to determinism/* 

It is interesting to recognize that despite their differences in 
religious convictions, Bernard, who was probably an agnostic, 
and Pasteur, who was a practicing Roman Catholic, had arrived 
at essentially the same scientific philosophy. Both limited the role 
of experimental science in biology to the physicochemical deter- 
minism of living processes, but they accepted its power as su- 
preme within this restricted field. 

It is thus certain that many influences other than the Catholic 
dogma played a decisive part in shaping Pasteur's conviction that 
materialist doctrines are inadequate to account for the origin of 
life. Like most men, he believed that it was through spontaneous 
inner feelings and direct experience that he had arrived at the 
metaphysical and religious views which he expressed with such 
warmth and conviction. And indeed, sheltered as he was within 
the walls of his laboratory, coming into contact with the world 
almost exclusively through his dealings with objective scientific 
problems, he appeared protected from the whims and fluctuations 
of public thinking. But the currents of human thought are made 
of immensely diffusible stuff, and permeate the whole fabric of 
human societies; no walls are impermeable to them; they reach 
the peasant hearth as well as the inner rooms of scientific sanctu- 
aries. Hegelian logic compounded with positive science, Catholic 
faith tempered by the intellectual philosophy of the eighteenth 


century, physicochemical interpretation of living processes col- 
ored with a touch of emergent evolution and elan vital all these 
influences and probably many others had found their way into 
Pasteur's mind while he was working over his microscope and 
injecting his animals. It was through a mistaken illusion, such as 
he was so fond of detecting in others, that he came to regard his 
beliefs as spontaneous generations of his heart. 

Pasteur did not intend to propound a philosophical doctrine 
when he emphasized with such intensity the limitations of experi- 
mental science. He meant only to state that Creation is more vast 
than what is revealed by our senses, even with the aid of scien- 
tific insight and instruments. The universe certainly transcends 
the concepts devised by the human mind to imagine that which 
cannot be seen, and it is because men perceive only a very small 
angle of reality that they often disagree so profoundly. In the 
search for truth, tolerance is no less essential than objectivity and 
sincerity. Pasteur will be remembered for having contributed his 
stone to the great edifice of human understanding, but it is for 
simpler reasons that he labored and that his name is now hon- 
ored. If he devoted himself to science with so much passion, it 
was not only for the sake of interest in philosophical problems, 
but also because he found "enchantment" in the "serene peace of 
libraries and laboratories/* It was there also that he satisfied the 
romantic urges of his enthusiasm, of that inner god which made 
him regard each experiment as a miracle, each conflict as a 

With struggle, but with great success, he served through his 
eventful life many of the deities worshiped by thinking men. He 
used the experimental method to create for humankind the wealth, 
comfort and health which make our sojourn on earth more enjoy- 
able. He tried to answer by the techniques of science some of the 
eternal questions which have been asked in so many different 
forms by all civilizations. He even dared to attempt to create life 
anew, or to modify it, by his own artifices. And yet, throughout all 


these bold ventures where as much as any living man lie mani- 
fested the glorious conceit of the human race he retained, child- 
like, the creed and worshipful attitude of his ancestors. His life 
symbolizes the hope that a time will come when the infallibility 
of the experimental method can be reconciled with the changing 
but eternal dreams of the human heart. 

Events of Pasteur's Life Arranged 
in Chronological Order 

1822: Birth of Louis Pasteur at Dole on December 27. 

1827: Removal of Ms family to Arbois. 

1838: Trip to Paris in October with plan to study at the Institution 


Return to Arbois with his father in November. 

1842: Secondary education at the College Royal de Resancon. 
1842: First admission to the Ecole Normale Superieure in Paris, 

and resignation in hope of achieving better rank. 

1843: Completioa-tff^secondary studies at the Lycee Saint-Louis, 

at the Sorbonne and at the Institution Barbet in Paris. 
1843: Readmission to the Ecole Normale, fifth in rank. 

1846: Beginning of chemical and crystallographic studies, as a 

student at the Ecole Normale. 

Discovery of molecular asyrnmetry. 

1846: Appointment as assistant to Balard, at the Ecole Normale. 
1847: Completion of requirements for doctorate es-sciences. 
1848: Appointment as professor of chemistry at the Universite de 

1849: Marriage to Marie Laurent, daughter of the Rector of the 

University, on May 29. 
1850: Birth of his daughter Jeanne. 
1851: Birth of his son Jean-Baptiste. 
1853: Birth of his daughter C6cile. 

Prix de la Soci6t& de Pharmacie de Paris for the synthesis of 

racemic acid. 

Award of Legion of Honor. 
1854: Appointment as professor of chemistry and dean in the newly 

organized Facult6 des Sciences at Lille. 
1855: Beginning of studies on fermentation. 
1857: Publication of the Memoire sur la fermentation appelee lac- 


Rumford Medal from the Royal Society of London for his 

studies on crystallography. 


Appointment as manager and director of scientific studies at 

the Ecole Normale Superieure in Paris. 
1858: Birth of his daughter Marie-Louise. 
1859: Death of his daughter Jeanne in September at Arbois. 

Beginning of studies on spontaneous generation. 

Prix de Physiologie Experimentale (Academie des Sciences) . 
1860: Publication of the Memoire sur la fermentation alcoolique. 

Two lectures before the Societe Chimique de Paris on 

"Recherches sur la dissymetrie moleculaire des produits or- 

ganiques naturels" 
1861: Discovery of anaerobic life. 

Lecture before the Societe de Chimie, "Sur les corpuscules 

organises qui existent dans ^atmosphere. Examen de la doc- 
trine des generations spontanees." 

Prix Jecker (Academie des Sciences) for studies on fermen- 
1862: Election in December as a member of the Paris Academie 

des Sciences in the section of mineralogy. 

Studies on acetic acid fermentation. 

Prix Alhumbert for his studies on spontaneous generation. 
1863: Studies on wine. 

Appointment as professor of geology, physics and chemistry 

at the Ecole des Beaux Arts. 

Birth of his daughter Camille. * 
1864: Publication of the "Memoire sur la -fermentation acetique." 

Lecture at the Sorbonne on "Des generations spontanees." 

Controversy with Pouchet, Joly and Musset on spontaneous 


Establishment of a field laboratory for the study of wines 

in home of his school friend Jules Vercel in Arbois. 
1865: Studies on pasteurization. 

Beginning of studies on silkworm diseases, at Alais; con- 
tinued until 1869. 

Death of his father in June at Arbois. 

Death of his youngest daughter Camille in September 

(burial at Arbois) . 
1866: Publication of the Etudes sur le vin. 

Publication of an essay on the scientific achievements of 

Claude Bernard. 

Death of his daughter Cecile (burial at Arbois) . 
1867: Lecture in Orleans on manufacture of vinegar. 

Crand Prix of the Exposition Universelle of 1867 for method 

of preservation of wines by heating. 

Appointment as professor of chemistry at the Sorbonne. 

Resignation from his administrative duties at the Ecole 



1868: Publication of Etudes sur le vinaigre. 

Attack of paralysis (left hemiplegia) in October. 

Enlargement of laboratory at the Ecole Normale. 
1869: Resumption of studies on silkworm diseases, first at Alais, 

then on the estate of the Prince Imperial at Villa Vicentina 

1870: Publication of Etudes sur la maladie des vers a sole. 

Return to Paris, then to Arbois. Franco-Prussian War, 
1871: Trip from Arbois to Pontarlier in search of his son Jean- 

Baptiste of the French Army in retreat. 

Sojourn for a few months at Clermont-Ferrand; beginning of 

the studies on beer in Duclaux's laboratory. 

1877: Studies on beer and on fermentation, in Paris at the Ecole 

1873: Election as an associate member of the Academic de Mede- 

1874: Address on occasion of graduation exercises at the College 

d'Arbois, in August. 
1875: Establishment of a field laboratory at Arbois (again in Jules 

VerceFs home) for studies on fermentation. 
1876: Candidacy for election to the Senate. Defeat at the election. 

Publication of Etudes sur la biere* 
1877: Beginning of studies on anthrax. 
1878: Controversies (especially with Colin) on etiology of 


Studies on gangrene, septicemia, childbirth fever. 

Publication of the memoir La th6orie des germes et ses 

applications ti la medecine et a la chirurgie. 

Discussion of a posthumous publication of Claude Bernard, 

and controversy with Berthelot on fermentation. 
1879: Studies on chicken cholera. Discovery of immunization by 

means of attenuated cultures. 

Marriage of his daughter Marie-Louise to Ren6 Vallery- 


Marriage of his son Jean-Baptiste. 
1880: Beginning of studies on rabies. 

Publication of the memoir Sur les maladies virulentes et en 

particulier sur la maladie appelee vulgairement cholera des 

1881: Publication of studies on anthrax vaccination De la pos- 

sibilit6 de rendre les moutons rejractaires au charbon par la 

mSthode des inoculations preventives. 

Field trial of anthrax vaccination at Pouilly le Fort. 

Paper before the International Congress of Medicine in 

London on the studies on fowl cholera and anthrax 


"Vaccination in Relation to Chicken Cholera and Splenic 

1882: Election to the Academic Francaise and reception by Ernest 


Studies on cattle pleuropneumonia. 

Paper before the Congress of Hygiene at Geneva on "At- 
tenuation des Virus." 

Controversy with Koch on anthrax immunization. 

Studies on rabies. 
1883: Establishment of a laboratory at family home in Arbois. 

In July, official celebration at his birthplace and Pasteur's 

address to the memory of his parents. 

Vaccination against swine erysipelas. 

Studies on cholera (Death of Thuillier in Egypt), 

Lecture before the Societe Chimique de Paris "La dissy- 

metrie moUcuMre" 
1884: Studies on vaccination against rabies. 

Paper before the International Congress of Medicine in 

Copenhagen on "Microbes pafhogenes et vaccins" 
1885: Treatment of Joseph Meister and Jean Baptiste Jupille 

against rabies. 
1886: Establishment of kennels for the study of rabies in dogs at 

Garches (Villeneuve FEtang). 

International subscription for the foundation of an Institut 

Pasteur, devoted to the study and treatment of rabies and 

other microbiological problems (Pasteur Institute). 

Controversies on rabies. 

Convalescence for a few weeks at Villa Bischoffheim, Bor- 

dighera. Return to Paris to answer attacks against rabies 


1887: Report of the English commission on rabies. 
1888: Inauguration of the Pasteur Institute on November 14. 
1892: Pasteur Jubilee at the Sorbonne on December 27. 
1894: Last stay at Arbois (July to October). 
1895: Death on September 28 at Villeneuve TEtang. 


Detailed information concerning the events of Pasteur's life can be 
found in the following publications: 

DUCLAUX, E. 1 : "Le Ldboratoire de M. Pasteur." In Centieme An- 

niversaire de la Naissance de Pasteur. (Institut Pasteur, Paris: 

Hachette, 1922.) 
DUCLAUX, MADAME E.: La Vie de Emtte Duclaux. (Paris: L. Barneoud 

&Cie., 1906.) 
LOIR, A. 2 : A Pombre de Pasteur. In Mouvement Sanitaire. Vol. 14 

(1937), pp. 43, 84, 135, 188, 269, 328, 387, 438, 487, 572, 619, 

659; Vol. 15 (1938), pp. 179, 370, 503. 
Pasteur, Correspondance reunie et annotee par Pasteur ValLery-Radot 3 

(Paris: Bernard Grasset, 1940.) 
Pasteur, Dessinateur et Pastelliste (18361842}. Compiled by Rene 

Vallery-Radot. (Paris: Emile Paul, 1912.) 
Roux, E. 4 : "L'Oeuvre Medicale de Pasteur" In Centieme Anniversaire 

de la Naissance de Pasteur. (Institut Pasteur, Paris: Hachette, 


VALLERY-RADOT, R. 5 : La Vie de Pasteur. (Paris: Hachette, 1922.) 
VALLERY-RADOT, R.: Madame Pasteur. (Paris: Flammarion, 1941.) 

1 Duclaux became Pasteur's assistant in 1862 and remained his close 
associate to the end. He was the first director of the Pasteur Institute after 
Pasteur's death. 

2 Loir was Pasteur's nephew and was his technical assistant between 
1884 and 1888. 

3 Pasteur's grandson. 

4 Roux became Pasteur's assistant in 1876 and became director of the 
Pasteur Institute in 1904. 

5 Pasteur's son-in-law. 


All of Pasteur's publications as well as a large number of unpub- 
lished manuscripts and notes have been collected in: 

Oeuvres de Pasteur, runies par Pasteur Vattery-Radot 
(Paris: Masson et Cie., 1933-1939) 



I. Dissymetrie moleculaire 
II. Fermentations et generations dites spontanees 

III. Etudes sur le vinaigre et sur le vin 

IV. Etudes sur la maladie des uers a sole 
V. Etudes sur la biere 

VI. Maladies virulentes, virus-vaccins et prophylaxie de 

la rage 
VII, Melanges sdentifiques et litteraires 

The development of Pasteur's scientific work has been lucidly and 
critically analyzed in: 

DUCLAXIX, E.: Pasteur. Histoire Sun esprit 
(Sceaux: Charaire et Cie., 1896.) 


The views expressed in the present volume concerning the influence 
of historical factors, and of the scientific and social environment, on 
the unfolding of Pasteur's career are based on information derived 
from the following sources: 

AGKERJSKECHT, E. H.: Anticontagionism between 1821 and 1867. 
(Bull of Hist, of Med. 1948, 22, 562-593.) 

AYKROYD, W. R.: Three Philosophers. (London: William Heinemann, 

BALLANTINE, W. G.: The Logic of Science. (N. Y.: Thomas Y. 
Crowell Co., 1933.) 

BEDIER, J. et HAZABD, P.: Histoire de la Litterature Fmngaise lUustre'e. 
(Paris: Larousse, 1924.) 

BEKNAL, J. D.: The Social Function of Science. (London: George 
Routledge & Sons, Ltd., 1939.) 

BERNARD, C.: An Introduction to the Study of Experimental Medi- 
cine. (N. Y.: The Macmillan Co., 1927.) 

BROWN, H.: Scientific Organizations in Seventeenth-Century France. 
(Baltimore: The Williams & Wilkins Co., 1934.) 

BXILLOCH, W.: The History of Bacteriology. (London: Oxford Univer- 
sity Press, 1938.) 

CASTIGLIONI, A.: A History of Medicine. (N. Y., A. A. Knopf, 1941.) 

COHEN, I. B.: Science., Servant of Man. (Boston, Little, Brown and Co., 

CONANT, J. B.: On Understanding Science: an Historical Approach. 
(New Haven: Yale University Press, 1947.) 

CROWTHER, J. G.: British Scientists of the Nineteenth Century. 
(London: George Routledge & Sons, 1935.) 

: Famous American Men of Science. (N. Y.: W. W. Norton & 

Co., 1937.) 


CROWTHER, J. G.: The Social Relations of Science. (N. Y.; The Macmil- 
Ian Co., 1941.) 

DAMPIER, W. C. D.: A History of Science and Its Relation witk 
Philosophy and Religion. (N. Y.: The Macmillan Co., 1930.) 

DRACHMAN, J. M.: Studies in the Literature of Natural Sciences. 
N. Y.: The Macmillan Co., 1930.) 

FRANKLAND, P. F. and FRANKLAND, MRS. P.: Pasteur. (N. Y. The 
Macmillan Co., 1898.) 

GARRISON, F. H.: An Introduction to the History of Medicine. (Phila.: 
W. B. Saunders Co., 4th edition, 1929.) 

GODLEE, R. J.: Lord Lister. (London, Macmillan & Co. Ltd., 1918.) 

GOLDENWEISER, A.: Robots or Gods. (N. Y.: A. A. Knopf, 1931.) 

GREENWOOD, M.: Epidemics and Crowd-Diseases. (London: Wil- 
liams & Norgate Ltd., 1935.) 

GREGORY, J. C.: The Scientific Achievements of Sir Humphry Davy. 
(London; Oxford University Press, 1930.) 

HAGGARD, H. W.: Devils, Drugs, and Doctors. (N. Y.: Harper, 1929.) 

HARDEN, A.: Alcoholic Fermentation. (London: Longmans, Green & 
Co., 3rd edition, 1923.) 

HARDING, R. E. M.: The Anatomy of Inspiration. (Cambridge, Eng- 
land: W. Heffer & Sons, 2nd edition, 1942.) 

HELMHOLTZ, H.: Popular Lectures on Scientific Subjects. Translated 
by E. Atkinson. First Series. (London: Longmans, Green & Co., 
Second Series. (London: Longmans, Green & Co., 1881.) 

HOGBEN, L.: Science for the Citizen. (N. Y.: A. A. Knopf, 1938.) 

HUME, E. E.: Max von Pettenkofer. (N. Y.: Paul B. Hoeber, Inc., 

HUXLEY, L.: Life and Letters of Thomas Henry Huxley. (N. Y.: 
D. Appleton Co., 2 vols., 1902.) 

KRAMER, H. D.: The Germ Theory and the Early Public Health Pro- 
gram in the United States. (Butt. Hist. Med. 1948, 22, 233-247.) 

LARGE, E. D.: The Advance of the Fungi. (London: Jonathan Cape, 

LAVOISIER, A. L.: Oeuvres de Lavoisier. (Paris: 4v. Imprimerie Im- 
periale, 1862-1868.) 

LEVY, H.: Modern Science A Study of Physical Science in the World 
Today. (N. Y.: A. A. Knopf, 1939.) 

MEAD, G. H.: Movements of Thought in the Nineteenth Century, 
edited by M. H. Moore (Chicago: University of Chicago Press, 

MEES, C. E. K.: The Path of Science. (N. Y.: John Wiley & Sons, 
Inc., 1946.) 

MERZ, J. T.: A History of European Thought in the Nineteenth Cen- 
tury. (London: William Blackwood & Sons, ed. 4 vol. I, ed. 3 
vol. II, 1923-1928.) 


MURRAY, R. H.: Science and Scientists in the Nineteenth Century. 

(N. Y.: The MacmiUan Co., 1925.) 
NEWMAN, G.: Interpreters of Nature. (London: Faber & Gwyer, 

NEWSHOLME, A.: Evolution of Preventive Medicine. (Baltimore: 

Williams & Willdns Co., 1927.) 
NORDENSKIOLD, E.: The History of Biology; a Survey. (N. Y.: A. A. 

Knopf, 1932.) 
OLMSTED, J. M. D.: Claude Bernard, Physiologist. (N. Y.: Harper, 

: Francois Magendie, Pioneer in Experimental Physiology and 

Scientific Medicine in XIX Century France. (N. Y.: Henry 

Schuman, 1944.) 
PACK, G. T. and GRANT, F. R.: The Influence of Disease on History. 

(Bull. N. Y. Academy Medicine, 1948, 24, 523-540.) 
PLEDGE, H. T.: Science Since 1500. (London: His Majesty's Stationery 

Office, 1939.) 

PORTERFEELD, A. L.: Creative Factors in Scientific Research. (Dur- 
ham: Duke University Press, 1941.) 
ROBINSON", V.: Pathfinders in Medicine. (N. Y.: Medical Life Press, 

2nd edition 1929.) 

SARTON, G.: The Life of Science. (N. Y.: Henry Schuman, 1948.) 
SHENSTONE, W. A.: Justus von Liebig, His Life and Work. (London: 

Cassell & Co., Ltd., 1901.) 
SHRYOCK, R. H.: The Development of Modern Medicine. (N. Y.: 

A. A. Knopf, 1947.) 
SINGER, C.: A Short History of Medicine. (N. Y.: Oxford University 

Press, 1928.) 
STEARN, E. W. and STEARN, A. E.: The Effect of Smallpox on the 

Destiny of the Amerindian. (Boston: Bruce Humphries, Inc., 


THORNTON, J. E.: Science and Social Change. (Washington: Brook- 
ings Institution, 1939.) 

TYNDALL, J.: Fragments of Science. (N. Y.: Appleton, 2v., 1896.) 
TYNDALL, J.: New Fragments. (N. Y.: Appleton, 1896.) 
WALLACE, A. R.: The Wonderful Century. Its Successes and Its 

Failures. (N. Y.: Dodd, Mead & Co., 1899.) 
WEBSTER, L. T.: Rabies. (N. Y.: The Macmillan Co., 1942.) 
WHITEHEAD, A. N.: Science and the Modern World. (N. Y.: The 

Macmillan Co., 1925.) 
WIEGAND, W. B.: Motivation in Research. (Chem. and Eng. News, 

1946, 24, 2772-2773.) 
WINSLOW., C. E.: The Conquest of Epidemic Disease. (Princeton: 

Princeton University Press, 1943.) 
WOLF, A.: A History of Science, Technology and Philosophy in the 

Eighteenth Century. (London: Allen & Unwin Ltd., 1938.) 




Academic Franc. aise (Academy of 
Letters), 50, 333, 355, 377, 385, 
387, 391. 

Academy of Medicine, 48, 74-75, 
185-186, 189, 248, 260-261, 263, 
284-287, 301, 304, 324-325, 327, 
335, 345-548. 

Academy of Sciences, 6, 8-10, 14, 
34, 37, 40, 42-43, 45, 73, 92, 108, 
121, 165, 173-174, 176, 182, 198, 
220, 357. 

Acetic acid fermentation, 116, 137 
141, 144, 161. 

Adaptation, see Virulence, alterations 

Adaptive enzymes, 383. 

Aerobic life, 136. See also Respira- 

Alais, 30, 52, 215-232. 

Alcoholic fermentation, 73, 115-126, 
129, 148, 161, 182-186, 191-208, 

Aleppo boil, 300. 

Alhumpert Prize, 166, 173. 

Ampere, Jean-Jacques, 7, 12, 153. 

Amyl alcohol, 115, 125, 126. 

Anaerobic life, 45, 135, 136, 188- 
190, 257, 360, 372. See also Fer- 

Analogy, use of, in scientific dis- 
covery, 138, 327, 373-374. 

Anthrax, 48, 67, 68, 73, 81, 234, 240, 
244, 249, 250-256, 258, 260-261, 
266, 272-276, 284, 289, 309, 330- 
331, 337-343, 357, 380. 

Antisepsis, 48, 128, 151, 245, 300- 

Appert, Frangois, 10. 

Arago, Dominique-Francois, 16, 99. 

Arbois, 21-22, 24, 28, 37, 45, 51, 68, 
143-144, 146, 184, 332, 349, 391. 

Aseptic techniques, 150, 301-302. 

Asparagine, 104, 108. 

Aspartic acid, 104, 10&-109. 

Assistants, see Pasteur's assistants. 

Asymmetry, molecular, 4CM1, 47, 
88, 90-115, 373; relation to living 
processes of, 108, 378-379. 

Attenuation of virulence, 281, 329- 
334, 355, 374. 

Australia, 310, 312. 

Autoclave, 179. 

Auzias-Turenne, 32^-326, 354. 


Bacon, Francis, 6, 10, 90, 188, 209, 
313, 362, 366-367. 

Bacteriological warfare, 312-313, 

Bacteriology, 49, 157, 189, 209; de- 
velopment of techniques, 186-187. 
See also Golden era o bacteri- 

Bacteriotherapy, 309-310, 380-381. 

Bail, Karl, 191-192. 

Balard, Antoine Jerome, 31-32, 34- 

35, 42, 91, 97, 16&-169. 
Bassi, Agostino, 209, 240, 258. 
Bastian, Henry Charlton, 72, 176, 

178-179, 185. 
Beer, studies on, 47, 68, 84, 147- 

150, 246, 361. 

Berkeley, Miles Joseph, 259-260. 
Bernard, Claude, 14, 16, 19, 30, 50, 

61, 72, 181, 241, 269, 358, 387, 

395, 398; posthumous publication, 

182-186, 198-208. 
Bert, Paul, 16, 182, 253, 256. 
Berthelot, Marcellin, 72, 123, 182, 

198-208, 386, 390, 395. 
Berthollet, Claude Louis, 9. 
Bertin-Mourot, Pierre Augustin, 28, 

36, 60, 68, 148. 



Berzelius, Jons Jakob, 117, 119, 121, 
123, 129, 137, 139, 155, 156, 198, 
199, 203. 

Bezancon, 17, 21, 36. 

Billroth, Albert Christian T., 247. 

Biochemical memory, 328-329. 

Biochemical sciences, 9, 133, 187- 

Biochemical unity of living proc- 
esses, 48, 153, 188-208, 379. 

Biological sciences and technology, 
141, 144^145, 153, 155, 380. 

Biological warfare, see Bacteriolog- 
ical warfare. 

Biot, Jean Baptiste, 34-35, 37, 41, 
43, 46, 90-92, 97, 102, 104, 108, 
115, 166. 

Bonn, diploma from University of, 

Botrytis bassiana, 209. 

Boussingault, Jean Baptiste, 30. 

Boyle, Robert, 237-238, 243. 

Boylston, Zabdiel, 320. 

Brauell, J. F., 251-252, 253. 

Bretonneau, Pierre, 239. 

Briicke, Ernst von, 243. 

Biichner, Hans, 156, 201-202. 

Budd, William, 305. 

Butyric acid fermentation, 45, 116, 
123, 134-136, 188-190, 195, 244, 
247, 251, 257, 372. 


120-121, 123, 203, 239. 
California wine maker, 152. 
Cancer, Pasteur's views on, 284. 
Cantoni, Gaetano, 213, 216, 219. 
Carlsberg laboratory, 148. 
Carnot, Sadi, 7, 368. 
Carriers of infection, 270, 278-279, 


Catalysis, 117, 119, 137. 
Chadwick, Edwin, 295-297. 
Chamberland, Charles Edouard, 61, 

66, 69, 75, 178, 261, 338, 340- 

Chance and scientific discovery, 19, 

95, 100-101, 106, 201, 368. See 

also Pasteur's luck. 
Chapin, Charles V., 307. 
Chappuis, Charles, 18, 28-29, 33, 40, 

43, 125. 

Chartres, 276. 

Chateaubriand, Frangois Rene, 15. 

Chemical processes of life, 9, 41, 

108, 110-115, 123, 190-208; basis 

of disease, 289-291, 382; basis 

of immunity, 354-358. 
Chemical vaccine, see Vaccinating 

Chemotherapy, 307-310. See also 

Chevreul, Michel Eugene, 174. 
Chicken cholera, 261, 272, 277- 

282, 289, 311, 327-330, 354-355, 


Childbirth fever, 261, 303. 
Cholera, 241, 250, 268-272. 
Clemenceau, Georges, 347348. 
Cohn, Ferdinand, 122, 179, 247, 

250, 253, 280. 
Colbert, Jean Baptiste, 6. 
Coleridge, Samuel Taylor, 12. 
Colin, G., 73, 74, 75, 284-287. 
College de France, 35, 98, 387. 
Columella, 236. 

Commercial exploitation of discov- 
eries, 69, 80-81, 341. 
Common sense, use in science of, 

248, 397. 

Comte, Auguste, 387-388, 392. 
Contagion, mechanisms of, 267-291. 
Contagious diseases, 48, 69, 107, 

209-316. See also Diseases. 
Controversies, see Pasteur. 
Cowpox, 300, 320-324, 327, 329. 
Creighton, Charles, 323. 
Crystal repair, analogy of, with 

wound healing, 125. 
Crystallography, 33-34, 73, 90-115, 

360, 370, 378. 
Cuvier, Georges, 13-14, 16. 
Cycle of matter in nature, 159, 


DAGUEBBE, Loins, 8, 31. 

Darwin, Charles, 14, 16-17, 76, 277, 

292, 366-368. 
Davaine, Casimir Joseph, 244, 251- 

254, 256, 274. 
Davy, Humphry, 8, 12-13, 16, 83, 


Delafond, Onesime, 251. 
Delafosse, Gabriel, 32, 91, 92. 



Dessaignes, Victor, 108. 

Deville, Sainte-Claire, see Sainte- 

Dijon, 35. 

Discovery, see Scientific discovery. 
Disease, chemical basis of, 289-291; 

mechanism of, 267-291; study of, 

46, 48, 361, 380. 
Disease as physiological conflict, 


Diseases of fermentation, 144r-154. 
Diseases of filth, 295-297, 304-305. 
Dole, 3, 22, 24. 
Domestication of microbial life, 


Du Bois-Reymond, Emil, 243. 
Duclaux, Emile, 21, 59, 63, 70, 73, 

81, 113-114, 148, 168, 193, 196, 

208, 210, 213, 214, 217, 220, 223, 

263, 382. 
Dumas, Jean Baptiste, 16, 29, 30-31, 

35, 41, 43, 46, 50, 58, 59, 81, 

118, 166, 168, 203, 213. 
Duruy, Victor, 15. 
Dusch, Theodor von, 164. 
Dust, as carrier of microorganisms, 

179-180, 235-236, 245-246. 

EAUTHCWORMS, 14, 275-277, 371. 
Ecole des Beaux Arts, see School of 

Fine Arts. 
Ecole Normale Superieure, 17, 26, 29, 

31-32, 36, 42, 62, 69, 81, 90, 95, 

216, 360. 

Economy of matter, 159, 360. 
Edelfeldt, 26, 334. 
Edison, Thomas A., 19. 
Egg-selection method, 68, 216-232. 
Ehrenberg, Christian, 122. 
Einstein, Albert, 364. 
Encyclopedists, 6, 393. 
Energy in biochemical processes, 

19^197, 372. 
English commission investigating 

rabies, 349-352. 
Enthusiasm, 23, 392. 
Environmental factors, influence on 

susceptibility to disease of, 314- 


Enzymes, 199-208, 379. 
Epidemic climate, 270. 

Epidemics, 46, 209, 267-291, 294; 

empirical control of, 292-299. 
Epidemiology, 49, 230-232, 234- 

235, 256, 278, 282. 
Exhaustion theory of immunity, 353 

Experimental method, 56, 74, 131, 

362, 376-377, 387-389, 396. 

FARABAY, MICHAEL, 5, 7, 12-13, 16, 
19, 50, 364-365, 367, 392-394. 

Fechner, Gustav, 397. 

Fermentation, 41, 48, 67, 73, 90, 
106-107, 114, 116-117, 119, 160, 
164, 187, 189-208, 247, 301, 360, 
379; analogy of, with disease, 48, 
214, 233, 237-239; and respira- 
tion, 194-208; diseases of, 144- 
154; mechanisms of, 118-159, 
372; relation of, to muscle me- 
tabolism, 196. See also individual 
fermentations ( acetic, alcoholic, 
butyric, lactic, tartaric). 

Fermentation correlative with life, 
43, 12&-134, 189-208. 

Fermentation in synthetic media, 
130-133, 157, 205. 

Fermentation is life without air, 

Ferments, 117, 127, 133, 190-208. 

Filterable viruses, 225, 264r-266. 

Filth and disease, 295-297, 304-305. 

Filtration and removal of germs, 
164, 170, 178-179, 255, 290. 

Flacherie, 212, 221-232, 247, 371. 

Flaming, use of, for sterilization, 

Flourens, Marie Jean Pierre, 173. 

Fortoul, Hippolyte, 18. 

Fourcroy, Antoine Frangois, 9. 

Fracastoro, 237. 

Franco-Prussian War, 47, 51, 77-78, 

FranHin, Benjamin, 32. 

GALILEO, 4, 41, 390. 
Garches, 69. 

Garrison, Fielding H., 295. 
Gattine, 212, 221-232. 
Gauss, Karl Friedrich, 364-365. 
Gay-Lussac, Joseph Louis, 118, 120, 
129, 171, 203. 



Genius, 87-88, 382, 385. 

Geoffrey Saint-Hilalre, Etienne, 5, 
14, 16. 

Germs In air, 170-187. 

Germ theory, 41, 44, 72. 

Germ theory of disease, 41, 48, 75, 
107, 115, 161, 233-266; of fer- 
mentation, 41, 47, 72, 115-208, 

Gernez, Desir Jean Baptiste, 53, 
105, 217, 220. 

Goethe, Johann Wolfgang von, 124, 

Golden era of bacteriology, 260-261, 

Grancher, Jacques Joseph, 62, 335, 
345, 347. 

Greenwood, Major, 322, 324. 

Grosvenor, Robert, 323. 

Grove, William Robert, 367. 

HARVEY, WILUAM, 5, 159. 

Haiiy, Rene Just, 91, 99. 

Hay bacillus, 254. 

Hay bacillus in anthrax vaccine, 341. 

Heat, effects of, 120, 151, 164, 166, 

168-169, 178-179. 
Hegel, Georg, 396. 
Helmholtz, Hermann von, 7, 13, 16, 

122-123, 165, 168, 243, 248, 363, 

368, 392, 394. 
Hemihedral facets, 91. 
Henle, Jacob, 240. 
Henle-Koch postulates, 240, 266. 
Henry, Joseph, 7, 10, 367. 
Hereditary susceptibility to disease, 

230-232, 314-316. 
Herschel, John, 91, 92. 
Heterogenie, 166. 

Hippocratic medicine, 236, 313-314. 
Holmes, Oliver Wendell, 261, 303- 


Host-parasite relationships, 273. 
Humboldt, Friedrich von, 13. 
Huxley, Thomas Henry, 14, 16, 76, 

180, 366. 

Hydrophobia, see Rabies. 
Hygiene, 270-271, 292-316. 

IMMUNITY, 49, 261, 284, 299, 317- 
358, 361, 373; chemical basis of, 
381; mechanisms of, 353-358. 

Infection, carriers of, 180, 270. 
Infectious diseases, see Contagious 

Infinitely small, the, 17, 45, 162, 


Insect vectors, 298. 
Interference phenomenon, 357. 
Intuition in scientific discovery, 131, 

133, 154, 219, 359-360, 362, 365- 

367, 371. 
Isomerism, 98, 106. 

JACOBSEN, J. C., 148. 

Jaillard, Pierre Frangois, 252, 254, 


Jefferson, Thomas, 317, 323. 
Jenner, Edward, 300, 317-324, 327- 

328, 331, 336, 373. 
Johnson, Dr. Samuel, 382. 
Joly, Nicolas, 173. 
Joubert, Jules Francois, 60, 178, 233. 
Joule, James Prescott, 7, 368, 392. 
Jupille, Jean Baptiste, 49, 53, 69, 

336, 345. 
Juvenal, 233. 


Kekule, Friedrich August, 363-364, 

Kelvin, Lord (William Thompson), 

7, 19, 363, 367, 392. 
Koch-Henle postulates, 240, 266. 
Koch, Robert, 48, 73, 240, 249-250, 

253-254, 257, 260-261, 269-271, 

274, 280, 306, 324-325, 341-342, 

Kiitzing, Friederich Traugott, 120- 

121, 123, 139, 203, 239. 


123, 125-126, 133, 245. 
Laennec, Rene T. H., 15. 
Laplace, Pierre Simon, 11. 
Large, E. D., 260. 
Laurent, Auguste, 91. 
Laurent, Marie, see Pasteur, Mme. 

Lavoisier, Antoine Laurent, 4, 8, 9, 

118-119, 129-130, 160, 203. 
Leblanc, Nicolas, 10. 
Lechartier, Georges Vital, 195. 
Leeuwenhoek, Anton van, 122, 238. 



Leonardo da Vinci, 58. 

Leplat, F., 252, 254, 256. 

Leprosy, 293. 

Liebig, Justus von, 9, 13, 30, 72, 81, 

121-132, 137, 139, 140, 144, 154- 

157, 197-208, 243, 248, 287, 358. 
Life, origin of, 40, 47, 111-115, 162, 

166, 177, 181, 187, 395-396. 
Lille, 18, 41-42, 112, 116, 124-125, 


Lindley, John, 259-260. 
Lister, Joseph, 48, 244-247, 301. 
Littre, Emile, 50, 386-388. 
Living processes, chemical unity of, 

48, 135, 188-208, 379. 
Living processes and chemistry, 9, 

30, 41, 108, 110-115, 119. 
Logic and scientific discovery, 131, 

138, 222, 359, 375. 
Loir, Adrien, 60, 62, 65, 79, 81, 87, 

302, 310-312, 326, 333-334, 375. 
London, Great Stench of, 305-306; 

Pasteur's visit to brewery in, 148 

Ludwig, Karl, 243. 



Magendie, Francois, 363. 
Malaria, 294-295, 298. 
Malic acid, 104-105, 109. 
Marat, Jean Paul, 11. 
Marggraf, Andreas Sigismund, 8. 
Marx, Karl, 18. 
Mather, Cotton, 320, 323. 
Mathilde, Princess, 15. 
Maxwell, Clerk, 15, 364-365, 392, 

Meister, Joseph, 49, 53, 69, 335- 

336, 344r-345, 349. 
Melun, 49, 67, 338. 
Mendelejeff, Dmitrij, 368. 
Mesotartaric acid, 104, 109. 
Metchnikoff, Elie, 272. 
Meyer, Lothar, 368. 
Meze, 153. 
Microbe, 188. 

Microbiology, see Bacteriology. 
Microorganisms, 41, 189; activities 

of, affected by environment, 145. 

See also Germ theory. 

Mitscherlich, Eilhardt, S3, 92-97, 

Molecular configuration, 40, 90-115, 

193, 360. 

Monge, Gaspard, 10. 
Montagu, Lady, 319. 
Montaigne, Michel de, 317. 
Morphology, Pasteur's interest in, 

193-194, 263. 
Morphology as guide to study of 

functions, 192-194. 
Morse, Samuel F. B., 7. 
Morts fats, 212, 221-232. 
Motility of microorganisms, 134- 


Mucor mucedo, 191-192. 
Munich, 271. 
Muscle metabolism, 196. 
Musset, Charles, 173. 
Mycoderma aceti, 138-141, 145- 

147, 157, 191; vini, 147. 

NAPOLEON I, 10-11. 

Napoleon III, 16-18. 

National Academy of Sciences, 10. 

Needham, John Turberville, 163. 

Newcomen, Thomas, 7. 

Newton, Isaac, 4, 40, 390, 393. 

Nicolle, Charles, 339. 

Niepce, Joseph Nicephore, 8. 

Nightingale, Florence, 248, 297. 

Nocard, Edmond Isidore Etienne, 

Nosema bombyces, 222. 

Nutritional concepts of parasitism, 
283284; requirements of micro- 
organisms and higher organisms, 
133, 145, 264-266, 353-354, 379; 
theories of disease and immunity, 


Oersted, Jean Christian, 7, 18. 

Office of Scientific Research and De- 
velopment, 10. 

Optical activity, crystal shape and 
physiological processes, 33-34* 39, 
90-115, 125-126, 370. 

Oriental sore, 299-300. 

Origin of life, see Life. 

Organs, 68, 139, 

416 INDEX 

Osimo, Marco, 213, 216. 
Osteomyelitis, 263. 


Parasitism, 239, 242, 267, 282-283, 

Paratartaric acid, 33-34, 40, 41, 

Pasteur Institute, 23, 53, 56, 70, 336, 

344, 355. 
Pasteur, Jean Joseph, 3, 24-25, 35, 

51, 83-84, 125. 

Pasteur, Madame Jean Joseph, 25. 
Pasteur, Madame Louis, 24, 36-41, 

46, 51-52, 66, 79, 88, 217, 227. 
Pasteur, Louis, assistants of, 43, 59 

60, 64-66, 79, 215; birth, 3; burial 
of, in chapel, 23, 57; character 
and temperament of, 13, 26-29, 
37-38, 42, 44, 50-54, 63, 73, 75- 
76, 103, 154, 156, 171, 173, 183, 
207, 214, 227-230, 337-338, 345, 
369-370, 395-400; children, 51, 
217; controversies, 44, 49, 67, 70- 
78, 153, 157, 173, 197-208, 228, 
284-287, 341, 345-349; daily Me, 
66, 79; death, 3, 56; education, 
25-26, 52; enthusiasm, 23, 53; 
experimenter, 44-45, 59-88, 101, 
114-115, 166, 207, 219, 226, 342, 
370-376; fame and honors, 16- 
17, 21-24, 40, 43, 51, 53-56, 83; 
family Me, 25, 27, 38, 51, 63, 
79; father, 3, 24-25, 35, 51, 83- 
84, 125; genius, 24, 87-88, 101, 
266, 382; illnesses, 47, 53, 56, 64, 

230, 347, 354, 357; interest in 
empirical practices, 143, 226, 

231, 276; intuition, 359, 360, 361, 
371; jubilee, 17, 54, 76, 80, 85; 
laboratories, 32, 40, 42, 43, 45, 

47, 60-62, 64, 68-70, 81, 146, 
215, 217, 227, 275-276, 370; 
legend, 21-57; letters, 27, 33-34, 
37-38, 40, 43, 51, 67, 71, 73, 80, 
103, 104, 125; logic, 360-362; 
luck, 100-101, 106, 219, 309, 327, 
340, 342; mannerisms, 79-80; 
marriage, 36-38; mother, 25; moti- 
vation, 28-30, 80-89, 361; paint- 
ings, 21, 25-26, 370; patriotism 
and public spirit, 28, 50-51, 56, 

77, 83-85; philosophy and re- 
ligious faith, 50, 54, 85, 166, 376- 
377, 385-400; promoter of sci- 
ence, 45-47, 49-50, 59, 68-70, 
140, 151-152, 227-230, 342-343; 
public debates and lectures, 15, 
44-45, 50, 53-54, 58, 70-71, 73, 
75, 78, 84, 87, 139, 177, 187, 
377, 387, 391; sequence of dis- 
coveries, 190, 233, 359-384; 
teachers, 28-33; technique, 64- 
65, 101; travels, 40, 103/148-149, 
230; use of microscope by, 64, 
65, 92, 135, 146, 149, 155, 170, 
216-218, 222, 226, 263, 371; 
views on physicians as scientists, 
61-62, 74-75, 249; views on 
theoretical and practical science, 
18-19, 67, 88, 156; wife, 24, 51; 
will and testament, 55. See also 
Appendix outlining events of his 
life in chronological order, 401 

Pasteurization, 23, 47, 68, 80, 151- 
154, 361. 

Pavlov, Ivan Petrovich, 328. 

Pebrine, 212-232, 371. 

Pelletier, Louise, 345. 

Perkin, William Henry, 110. 

Peter, Michel, 73, 246, 346, 348, 

Pettenkofer, Max Joseph von, 270- 
272, 297-298. 

Philosophy, influence of, on biolog- 
ical theories, 172-173, 177, 347. 

Phipps, James, 321. 

Phylloxera, 310. 

Physicians, Pasteur's views on, 61, 
74-75, 249. 

Physicochemical interpretation of 
living processes, 119, 122-124, 
133-134, 139, 154, 197-208, 243, 
358, 390, 395. 

Physiological state and its effect on 
disease, 225, 230-232, 236, 272, 
284r-291, 302, 314-316, 382. 

Plant diseases, 258-260. 

Pneumococcus, 263, 375. 

Poincare*, Henri, 364. 

Polarization of light, 33-34, 90-115, 
193, 360, 378. 

Pont Gisquet, 217, 227. 



Positivist philosophy, 50, 386-388, 

Potato blight, 259. 

Potentialities of living things, multi- 
ple, 377-384. 

Pouchet, Felix Axchirnede, 72, 165- 
177, 287. 

Pouilly le Fort, 15, 49, 331, 333, 
338-340, 342-343. 

Practical vs. theoretical science, 4, 
18, 19, 42, 47, 58, 67, 68, 86, 
162, 190, 359. 

Preconceived ideas and scientific dis- 
covery, 94, 96-97, 100, 109, 157, 
362, 369, 376. 

Preyer, W., 397. 

Priority, concern with, 73, 82-83, 

Prophylactic and therapeutic meas- 1 
ures, difficulty of establishing 
evaluation of, 323-324, 344r-353. 

Provostaye, Frederic de la, 92-96. 

Proust, Marcel, 328. 

Public health, 49, 270-271, 292- 

Puerperal fever, see Childbirth 

Putrefaction, 116-117, 122-136, 
160, 164-165, 168, 180, 187-188, 
301; analogy of, with fermenta- 
tion and disease, 48, 237-239, 


RABBITS, destruction of, by intro- 
duction of disease, 310-312. 

Rabies, 49, 53, 62, 69-70, 73, 263- 
266, 298-299, 326, 329, 332-334, 
344-358, 374. 

Racemic acid, 93, 97, 106. 

Raulin, Jules, 112, 133, 284. 

Rayer, Roger, 244, 251. 

Religion and science, 390-400. 

Renan, Ernest, 333, 377, 385-391. 

Reservoirs of infection, 270278, 

Respiration and fermentation, 194- 

Robespierre, Maximilien de, 11. 

Robin, Charles, 240. 

Rossignol, H., 337-338. 

Roux, Emile, 39, 61, 63, 65, 75, 88, 

201, 249, 261, 264-265, 269, 275, 
334-335, 338-340, 346-347, 355. 

Royal Institution, 6, 12-13, 392. 

Royal Society, 6, 238, 320, 322. 

Rubner, Max, 202. 

ETIENNE, 42, 241, 269. 

Saint-Cloud, 22, 56, 69. 

Salmon, David Elmer, 381. 

Sand, George, 15. 

Sanitarians, 295-297, 304-307. 

Scarlet fever, 294. 

School of Fine Arts, Pasteur teaches 
at, 50, 81, 270, 316. 

Schroder, Heimich, 164, 168, 248. 

Schiilze, Franz, 164. 

Schwann, Theodor, 120-123, 164, 
203, 239, 240. 

Science, popularity of, 11. 

Science, and country, 77, 84-85; and 
philosophy and religion, 85-86, 
390-400; and society, 1-20, 77- 
78, 84-85; in war, 10, 77. See also 
Practical, Theoretical. 

Scientific discovery, mechanisms of, 
29, 87, 93, 159, 359-384. 

Sedillot, Charles Emmanuel, 188. 

Semmelweis, Ignaz Philipp, 261, 

Shelley, Percy Bysshe, 359 

Silkworms, culture of, 210-212; 
studies on, 46, 53, 68, 209-232, 
247, 308, 315, 361. 

Smallpox, 249, 299, 317-324, 327, 

Smith, Stephen, 296. 

Smith, Theobald, 381. 

Snow, John, 241-242, 269, 322. 

Social sciences, 389-390. 

Sorboime, 31, 34, 81; Pasteur's 
jubilee at, 17, 54, 76, 80, 85; Pas- 
teur's lecture on spontaneous gen- 
eration at, 15, 177, 187. 

Spallanzani, Lazzaro, 163. 

Specificity, 107; basis of germ 
theory, 128-129, 133-134, 145, 
158, 166, 244, 264-266; of dis- 
ease, 145, 239, 242. 

Spectator, the, 23-24. 

Spencer, Herbert, 14. 



Spontaneous generation, 43-44, 72, Tyndall, Join, 13, 16, 165, 176, 
114, 159-187, 248, 347, 361, 395- 178-179, 181, 186, 354, 362, 394. 


TyndaHization, 180. 

Spores, 179, 253-254, 256, 274, 277, Typhoid fever, 271, 279, 306. 

330. Typhus, 295, 298. 

Staphylococcus, 262-263. 
Steam, W. E., 318. 
Stereochemistry, 90, 105. 
Stereoisomerism, 378. 

Strasbourg, 34, 36, 39, 103-104, 112. Vallery-Radot, Pasteur, 21. 
Streptococcus and puerperal fever, Vallery-Radot, Rene, 21, 75. 

261, 303. 

Streptococcus bombycis, 225. 
Surgery, see Lister, 
Swanneck flasks, 169, 175, 177. 
Swift, Jonathan, 267. 

Vaccination, 67-68, 273, 317-358, 

Variolation, 320-321. 

Vibrion septique, 252, 256-257, 

266, 287-288, 303, 341. 
Villemin, Jean Antoine, 347. 
ViHeneuve FEtang, 3, 56. 

Swine erysipelas, 68, 261, 272, 329, Vinegar studies, 45, 68, 136-141, 

331, 344. 
Sydenham, Thomas, 239. 
Symbiosis, 282-283. 

145-146, 246, 361. 
Virchow, Rudolph, 243. 
Virulence, alterations of, 280-282. 

Synthetic media, 130-133, 157, 205. Vitalistic theories, 121-122, 139, 
Syphilis, 237, 294, 324. 154-156, 189-208, 243, 358. 

Voltaire, 159, 163. 
TARTARIC ACIDS, 33-34, 41, 73, 92- Vulpian, Edme Felix Alfred, 335, 

113, 116, 193, 266. 346. 

Thenard, Louis Jacques, 102, 118, 

124, 129, 130, 132. 
Theoretical vs. practical science, 4, 

328, 368. 

18, 19, 42, 58, 67, 86, 162, 190, Waterhouse, Benjamin, 323. 


Watt, James, 7. 

Thermodynamics and living proc- Wheatstone, Charles, 7. 

esses, 195. 
Thompson, William, see Kelvin. 
Thomson, Arthur, 86. 
Thoreau, Henry D., 21. 
Thucydides, 326. 

Wilberforce, Bishop, 14. 

Wine studies, 45, 68, 141-153, 183, 

246-247, 361. 

Wohler, Friedrich, 8, 121, 123, 139. 
Wonderful Century, The, 17, 20. 

Thuillier, Louis Ferdinand, 269, 331, Working hypotheses, 62, 93, 101, 


Toxins, 273, 289-290, 355, 381. 

Transformations of microorganisms, 
191-193, 280, 328-333; of or- 
ganic matter, 41, 43; of virulence, Wiirtz, 60. 
see Attenuation. 

Traube, Moritz, 205. 

107, 109, 128, 361-367. 
Wound healing, analogy of, with 

crystal repair, 125. 
Wound infections, 300. 

YEAST, 48, 117, 120-121, 146, 149, 

Tuberculosis, 13, 250, 258, 293, 159-187, 189-208. 


Yellow fever, 298. 

Turpin, Pierre Jean Francois, 121, 
123, 203. ZYMASE, 201-202.